Beta Cell Apoptosis in NIDDM

Discussion in 'Food and nutrition' started by Quentin Grady, Nov 3, 2003.

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  2. Frank Roy

    Frank Roy Guest

    Quentin: Beta-cell apoptosis in the pathogenesis of human type 2 diabetes mellitus
    > http://www.eje.org/eje/149/0099/1490099.pdf
    I had some problem getting this article uploaded. I did some shenangigans by copying and pasting to
    Microsoft Word in order to get a printout of this article.

    This is a fairly comprehensive article. It is interesting that the vast majority of people do not
    develop type 2 diabetes and their endocrine pancreases are subject to the same biochemical
    processes.

    A good site for understanding the endocrine pancreas is at
    http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/pancreas/index.html

    The following article deals with more than the phamacological aspect of drugs and the mitochondria.
    There is a lot of good background material as well as links for recent research on the mitochondria.

    "Many important steps of lipid metabolism are located in mitochondria. Thus, formation of thioesters
    of CoA with fatty acids, i.e., the so-called "activation" of fatty acids that is the obligatory step
    in fatty acid metabolism, occurs partly in the endoplasmic reticulum and partly in the outer
    mitochondrial membrane (for long-chain fatty acids) or in the mitochondrial matrix (for medium-chain
    fatty acids). -Oxidation of fatty acids, the principal route of energy-yielding fatty acid
    catabolism, proceeds within the matrix compartment. Because the inner mitochondrial membrane is
    impermeable to acyl-CoA, long-chain fatty acyl-CoA formed in the outer mitochondrial membrane or in
    the endoplasmic reticulum must be transformed into the acylcarnitine ester. It then crosses the
    inner membrane and is transformed back to acyl-CoA on the inner side of the inner membrane. These
    processes are catalyzed by carnitine acyltransferases I and II (mostly represented by carnitine
    palmitoyltransferases I and II, abbreviated as CPT I and II) located in the outer membrane and the
    internal side of the inner membrane, respectively." Source: Mitochondria as a Pharmacological Target
    http://pharmrev.aspetjournals.org/cgi/content/full/54/1/101

    Frank
     
  3. Tcomeau

    Tcomeau Guest

    Quentin Grady <[email protected]> wrote in message
    news:<[email protected]>...
    > G'day G'day Folks,
    >
    > Some posters might find the following document useful.
    >
    > http://www.eje.org/eje/149/0099/1490099.pdf
    >
    > Best wishes,

    Interesting stuff. Here is an interesting quote:

    "A series of studies (33–36) report on the roles of high glucose concentrations and different free
    fatty acids (FFAs) on b-cell proliferation, apoptosis and function in cultured human islets. The
    results showed that A series of studies (33–36) report on the roles of high glucose concentrations
    and different free fatty acids (FFAs) on b-cell proliferation, apoptosis and function in cultured
    human islets. The results showed that prolonged exposure of cultured human islets to high glucose
    levels increased b-cell apoptosis in a dose-dependent manner. In addition, chronic exposure of
    cultured human islets to the saturated fatty acid palmitic acid results in increased markers of
    b-cell apoptosis and decreased b-cell proliferation. However, the mono-unsaturated fatty acids
    palmitoleic acid and oleic acid did not affect DNA fragmentation and induced b-cell proliferation.
    Moreover when co-supplemented, each of the monounsaturated fatty acids prevented apoptosis,
    prevented impairment of b-cell proliferation and improved insulin secretion that was caused by
    palmitic acid and/or hyperglycemia. In addition, chronic exposure of cultured human islets to the
    saturated fatty acid palmitic acid results in increased markers of b-cell apoptosis and decreased
    b-cell proliferation. However, the mono-unsaturated fatty acids palmitoleic acid and oleic acid did
    not affect DNA fragmentation and induced b-cell proliferation. Moreover when co-supplemented, each
    of the monounsaturated fatty acids prevented apoptosis, prevented impairment of b-cell proliferation
    and improved insulin secretion that was caused by palmitic acid and/or hyperglycemia."

    Repeat and partial quote: "prolonged exposure of cultured human islets to high glucose levels
    increased b-cell apoptosis in a dose-dependent manner."

    I don't think this could be any clearer. The more glucose b-cells were exposed to glucose and the
    higher the "dose" the more apoptosis (cell death) occurred. I gather that this is the
    not-so-mysterious-anymore glucotoxicity that we've heard about. This statement seems to indicate
    that there is a *direct* connection between blood sugar (glucose) levels and b-cell death.

    Repeat and partial quote: "In addition, chronic exposure of cultured human islets to the saturated
    fatty acid palmitic acid results in increased markers of b-cell apoptosis and decreased b-cell
    proliferation."

    Here we are told that *chronic* exposure to saturated fat cause increased *markers* of b-cell death
    and decreased b-cell proliferation. This isn't exactly saying that sat fat causes b-cell death but
    only causes an increase in "markers" of b-cell death. Can we assume that non-chronic exposures to
    saturated fat does not neceassarily lead to b-cell death or significant increase in markers of
    b-cell death?

    Repeat and partial quote: "the mono-unsaturated fatty acids palmitoleic acid and oleic acid did not
    affect DNA fragmentation and induced b-cell proliferation. Moreover when co-supplemented, each of
    the monounsaturated fatty acids prevented apoptosis, prevented impairment of b-cell proliferation
    and improved insulin secretion that was caused by palmitic acid and/or hyperglycemia."

    Mono-unsaturated fats prevented b-cell death and prevented b-cells from suffering impaired
    proliferation and it improved insulin secretion.

    In conclusion,

    1) Glucose impairs or kills b-cells directly dependent upon the dose of glucose. Note that all
    carbs in the diet are converted to glucose. The more the refined carbs the higher the blood
    glucose levels.

    2) Chronic levels of saturated fats cause some stress to b-cells.

    3) Mono-unsaturated fats protect and is necessary for the health of b-cells.

    Generally speaking, carbs cause b-cell death, fats protect against it.

    Interesting how the authors make the statements quoted above and then ignore the ramifications of
    their findings related to glucose and they spend most of their discussion on fats. Its right under
    their noses.

    TC
     
  4. Mike V

    Mike V Guest

    "Frank Roy" <[email protected]> wrote in message news:[email protected]...
    >
    >
    > Quentin: Beta-cell apoptosis in the pathogenesis of human type 2 diabetes mellitus
    > > http://www.eje.org/eje/149/0099/1490099.pdf
    > I had some problem getting this article uploaded. I did some shenangigans by copying and pasting
    > to Microsoft Word in order to get a printout of this article.
    >
    > This is a fairly comprehensive article. It is interesting that the vast majority of people do not
    > develop type 2 diabetes and their endocrine pancreases are subject to the same biochemical
    > processes.
    >
    > A good site for understanding the endocrine pancreas is at
    >
    http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/pancreas/index.html
    >
    > The following article deals with more than the phamacological aspect of drugs and the
    > mitochondria. There is a lot of good background material as well as links for recent research on
    > the mitochondria.
    >
    > "Many important steps of lipid metabolism are located in mitochondria. Thus, formation of
    > thioesters of CoA with fatty acids, i.e., the so-called "activation" of fatty acids that is the
    > obligatory step in fatty acid metabolism, occurs partly in the endoplasmic reticulum and partly in
    > the outer mitochondrial membrane (for long-chain fatty acids) or in the mitochondrial matrix (for
    > medium-chain fatty acids). -Oxidation of fatty acids, the principal route of energy-yielding fatty
    > acid catabolism, proceeds within the matrix compartment. Because the inner mitochondrial membrane
    > is impermeable to acyl-CoA, long-chain fatty acyl-CoA formed in the outer mitochondrial membrane
    > or in the endoplasmic reticulum must be transformed into the acylcarnitine ester. It then crosses
    > the inner membrane and is transformed back to acyl-CoA on the inner side of the inner membrane.
    > These processes are catalyzed by carnitine acyltransferases I and II (mostly represented by
    > carnitine palmitoyltransferases I and II, abbreviated as CPT I and II) located in the outer
    > membrane and the internal side of the inner membrane, respectively." Source: Mitochondria as a
    > Pharmacological Target http://pharmrev.aspetjournals.org/cgi/content/full/54/1/101
    >
    > Frank

    Frank: Thanks again for another of your detailed helpful posts. Always well resourced information
    uncluttered by dogmatic statements and rancor.

    MikeV
     
  5. Mike V

    Mike V Guest

    "Frank Roy" <[email protected]> wrote in message news:[email protected]...
    >
    >
    > Quentin: Beta-cell apoptosis in the pathogenesis of human type 2 diabetes mellitus
    > > http://www.eje.org/eje/149/0099/1490099.pdf
    > I had some problem getting this article uploaded. I did some

    >
    > Frank

    Note the follow up from one of the cited papers. MikeV

    Diabetes 52:726-733, 2003 © 2003 by the American Diabetes Association, Inc.

    Monounsaturated Fatty Acids Prevent the Deleterious Effects of Palmitate and High Glucose on Human
    Pancreatic ß-Cell Turnover and Function

    Kathrin Maedler1, José Oberholzer2, Pascal Bucher2, Giatgen A. Spinas1, and Marc Y. Donath1 1
    Division of Endocrinology and Diabetes, University Hospital, Zurich, Switzerland 2 Division of
    Surgical Research, Department of Surgery, University of Geneva Medical Center, Geneva, Switzerland

    Glucotoxicity and lipotoxicity contribute to the impaired ß-cell function observed in type 2
    diabetes. Here we examine the effect of saturated and monounsaturated fatty acids at different
    glucose concentrations on human ß-cell turnover and secretory function. Exposure of cultured human
    islets to saturated fatty acid and/or to an elevated glucose concentration for 4 days increased
    ß-cell DNA fragmentation and decreased ß-cell proliferation. In contrast, the monounsaturated
    palmitoleic acid or oleic acid did not affect DNA fragmentation and induced ß-cell proliferation.
    Moreover, each monounsaturated fatty acid prevented the deleterious effects of both palmitic acid
    and high glucose concentration. The cell-permeable ceramide analogue C2-ceramide mimicked both the
    palmitic acid-induced ß-cell apoptosis and decrease in proliferation. Furthermore, the ceramide
    synthetase inhibitor fumonisin B1 blocked the deleterious effects of palmitic acid on ß-cell
    turnover. In addition, palmitic acid decreased Bcl-2 expression and induced release of cytochrome c
    from the mitochondria into the cytosol, which was prevented by fumonisin B1 and by oleic acid.
    Finally, each monounsaturated fatty acid improved ß-cell secretory function that was reduced by
    palmitic acid and by high glucose. Thus, in human islets, the saturated palmitic acid and elevated
    glucose concentration induce ß-cell apoptosis, decrease ß-cell proliferation, and impair ß-cell
    function, which can be prevented by monounsaturated fatty acids. The deleterious effect of palmitic
    acid is mediated via formation of ceramide and activation of the apoptotic mitochondrial pathway,
    whereas Bcl-2 may contribute to the protective effect of monounsaturated fatty acids.
     
  6. Mike V

    Mike V Guest

    "tcomeau" <[email protected]> wrote in message
    news:[email protected]...
    > Quentin Grady <[email protected]> wrote in message
    news:<[email protected]>...
    > > G'day G'day Folks,
    > >
    > > Some posters might find the following document useful.
    > >
    > > http://www.eje.org/eje/149/0099/1490099.pdf
    > >
    > > Best wishes,
    >
    > Interesting stuff. Here is an interesting quote:
    >
    > "A series of studies (33-36) report on the roles of high glucose concentrations and different free
    > fatty acids (FFAs) on b-cell proliferation, apoptosis and function in cultured human islets. The
    > results showed that A series of studies (33-36) report on the roles of high glucose concentrations
    > and different free fatty acids (FFAs) on b-cell proliferation, apoptosis and function in cultured
    > human islets. The results showed that prolonged exposure of cultured human islets to high glucose
    > levels increased b-cell apoptosis in a dose-dependent manner. In addition, chronic exposure of
    > cultured human islets to the saturated fatty acid palmitic acid results in increased markers of
    > b-cell apoptosis and decreased b-cell proliferation. However, the mono-unsaturated fatty acids
    > palmitoleic acid and oleic acid did not affect DNA fragmentation and induced b-cell proliferation.
    > Moreover when co-supplemented, each of the monounsaturated fatty acids prevented apoptosis,
    > prevented impairment of b-cell proliferation and improved insulin secretion that was caused by
    > palmitic acid and/or hyperglycemia. In addition, chronic exposure of cultured human islets to the
    > saturated fatty acid palmitic acid results in increased markers of b-cell apoptosis and decreased
    > b-cell proliferation. However, the mono-unsaturated fatty acids palmitoleic acid and oleic acid
    > did not affect DNA fragmentation and induced b-cell proliferation. Moreover when co-supplemented,
    > each of the monounsaturated fatty acids prevented apoptosis, prevented impairment of b-cell
    > proliferation and improved insulin secretion that was caused by palmitic acid and/or
    > hyperglycemia."
    >
    > Repeat and partial quote: "prolonged exposure of cultured human islets to high glucose levels
    > increased b-cell apoptosis in a dose-dependent manner."
    >
    > I don't think this could be any clearer. The more glucose b-cells were exposed to glucose and the
    > higher the "dose" the more apoptosis (cell death) occurred. I gather that this is the
    > not-so-mysterious-anymore glucotoxicity that we've heard about. This statement seems to indicate
    > that there is a *direct* connection between blood sugar (glucose) levels and b-cell death.
    >
    > Repeat and partial quote: "In addition, chronic exposure of cultured human islets to the saturated
    > fatty acid palmitic acid results in increased markers of b-cell apoptosis and decreased b-cell
    > proliferation."
    >
    > Here we are told that *chronic* exposure to saturated fat cause increased *markers* of b-cell
    > death and decreased b-cell proliferation. This isn't exactly saying that sat fat causes b-cell
    > death but only causes an increase in "markers" of b-cell death. Can we assume that non-chronic
    > exposures to saturated fat does not neceassarily lead to b-cell death or significant increase in
    > markers of b-cell death?
    >
    > Repeat and partial quote: "the mono-unsaturated fatty acids palmitoleic acid and oleic acid did
    > not affect DNA fragmentation and induced b-cell proliferation. Moreover when co-supplemented, each
    > of the monounsaturated fatty acids prevented apoptosis, prevented impairment of b-cell
    > proliferation and improved insulin secretion that was caused by palmitic acid and/or
    > hyperglycemia."
    >
    > Mono-unsaturated fats prevented b-cell death and prevented b-cells from suffering impaired
    > proliferation and it improved insulin secretion.
    >
    > In conclusion,
    >
    > 1) Glucose impairs or kills b-cells directly dependent upon the dose of glucose. Note that all
    > carbs in the diet are converted to glucose. The more the refined carbs the higher the blood
    > glucose levels.
    >
    > 2) Chronic levels of saturated fats cause some stress to b-cells.
    >
    > 3) Mono-unsaturated fats protect and is necessary for the health of b-cells.
    >
    > Generally speaking, carbs cause b-cell death, fats protect against it.
    >
    > Interesting how the authors make the statements quoted above and then ignore the ramifications of
    > their findings related to glucose and they spend most of their discussion on fats. Its right under
    > their noses.
    >
    > TC

    TC: Good analysis. A point of the paper of course is that glucotoxicity requires *extended*
    hyperglycemic exposure, and something else has to get the apoptosis process started, possibly
    lipotoxicity. (As long as the pancreas can respond with more insulin, hyperglycemia does not arise)
    Regards MikeV
     
  7. Mike V

    Mike V Guest

    "Quentin Grady" <[email protected]> wrote in message
    news:[email protected]...
    >
    > G'day G'day Folks,
    >
    > Some posters might find the following document useful.
    >
    > http://www.eje.org/eje/149/0099/1490099.pdf
    >
    > Best wishes,
    >
    > --
    > Quentin Grady ^ ^ / New Zealand, >#,#< [ / \ /\ "... and the blind dog was leading."
    >
    > http://homepages.paradise.net.nz/quentin

    Hi Quentin: Useful overview on topic. regards MikeV

    JOP. J Pancreas (Online) 2002; 3(4):86-108. Islet Redox Stress: The Manifold Toxicities of Insulin
    Resistance, Metabolic Syndrome and Amylin Derived Islet Amyloid in Type 2 Diabetes Mellitus Melvin R
    Hayden1,2, Suresh C Tyagi3 1Department of Cardiovascular Atherosclerosis, Metabolism and Aging,
    Camdenton Community Health Center. Camdenton, Missouri, USA. 2Department of Family and Community
    Medicine, University of Missouri. Columbia, Missouri, USA. 3Department of Physiology and Biophysics,
    University of Mississippi Medical Center. Jackson, Mississippi, USA

    Page 1 of 23

    ABSTRACT Context Redox stress, reactive oxygen species, reactive nitrogen species, and oxygen free
    radicals ("toxic oxygen") are increasingly being reported as important cellular signaling
    mechanisms. It has been known for over a hundred years that type 2 diabetes mellitus is a manifold
    disease, not only in its etiology, but also in its associated manifold toxicities and multiple
    complications of the diabetic opathies. The presence of islet amyloid has also been described in
    association with type 2 diabetes mellitus for a century. Objective This review will attempt to
    remain focused on the relationship between redox stress, the reactive oxygen species and the
    reactive nitrogen species in the islet, and how these interact with the multiplicative effect of the
    toxicities of insulin resistance, metabolic syndrome, amylin (hyperamylinemia), amylin derived islet
    amyloid and type 2 diabetes mellitus. Conclusions Redox sensitive cellular signaling systems play an
    important role in the development, progressive nature (remodeling) and damaging effects on the beta
    cell within the islet of the pancreas. Furthermore, redox stress may play an important role in the
    remodeling and development of islet amyloid creating a space-occupying lesion with a resultant
    secretory and absorptive defect within the islet. The presence of manifold toxicities necessitates
    an approach of global risk reduction in the prevention and treatment of type 2 diabetes mellitus. An
    improved understanding of the dynamic relationship between these toxicities and redox stress within
    the islet will aid both the researcher and the clinician. BACKGROUND Transference of electrons
    between oxygen species (cellular respiration) allows each of us to survive on this planet, not only
    at the cellular level but also as an organism. Redox cycling describes the normal physiologic
    process of reduction and oxidation in order to pair anew unstable, damaging, reduced reactive oxygen
    species (ROS) which is meant to include the oxygen free radicals (O2 -: superoxide; H2O2: hydrogen
    peroxide; OH-: hydroxyl radical; singlet oxygen) and organic analogues which would include the
    reactive nitrogen species (RNS) which is primarily peroxynitrite (ONOO-). Redox cycling thus implies
    a homeostatic balance between ROS production and antioxidant capacity, and is also termed redox
    homeostasis. In contrast, redox stress (redox imbalance) implies a loss of this unique homeostasis
    with an excess production of ROS (Tables 1 and 2) either through the process of reduction or that of
    oxidation. Oxidative stress implies a loss of homeostasis

    Continued as:

    http://www.joplink.net/prev/200207/200207_02.pdf
     
  8. Mike S

    Mike S Guest

  9. Frank Roy

    Frank Roy Guest

    Mike V wrote:

    > Hi Quentin: Useful overview on topic. regards MikeV

    We can agree on that!
    >
    > JOP. J Pancreas (Online) 2002; 3(4):86-108. Islet Redox Stress: The Manifold Toxicities of Insulin
    > Resistance, Metabolic Syndrome and Amylin Derived Islet Amyloid in Type 2 Diabetes Mellitus Melvin
    > R Hayden1
    Dr. Hayden had this or perhaps another article that was published on MedScape.

    I had read that amyloid plaque would not form unless some other biochemical came from outside the
    pancreas. A year ago I posted a lot of links in ASD on this topic.
    http://groups.google.com/groups?hl=en&lr=&ie=UTF-8&selm=3DC87D6F.77B8D2E7%40erols.com

    As Quentin will mention occasionally, there are the genetic aspects as well as the environmental
    aspects involved in the cause of type 2 DM (my paraphrase, not his words). There are probably
    multiple causes of type 2. I believe that nutrition is the biggest factor that might tilt some
    genetic tendency into the T2 direction. Offspring of type 2 diabetics tend to have insulin
    resistance even before they have impaired fasting blood glucose.

    There has been some research on the exogenous AGE (advanced glycation end products). Much of this
    research has involved Helen Vlassara.

    "Diabetes is a major cause of morbidity and mortality in industrialized societies. Type 2 diabetes,
    the most prevalent form of diabetes, is characterized by resistance to the action of insulin in
    peripheral tissues and deficiency in insulin secretion by the pancreatic islet ß-cell. Insulin
    resistance (IR) is associated with progressive increases in fasting serum insulin levels and
    visceral adiposity in humans and in animal models. Nutrients, such as certain types of fat and
    carbohydrates, play a major role in the etiology of IR. Epidemiologic studies in Japanese and Pima
    populations demonstrate that populations with the same genetic background develop increased
    incidence of IR and type 2 diabetes whenever a " Western" lifestyle and diet is adopted.
    Furthermore, recent evidence suggests that nutrients can directly modulate insulin signaling and
    thus contribute to cellular IR independently from associated factors, such as physical activity,
    dyslipidemia, hypertension, and diabetes.

    Prolonged hyperglycemia leads to complications, such as vascular and renal disease. Under
    hyperglycemic conditions, endogenous nonenzymatic glycoxidation of proteins and lipids leads to the
    formation of heterogeneous products, collectively termed advanced glycation end products (AGEs).
    Many of the tissue changes observed in diabetic complications are attributed to their chemical,
    pro-oxidant, and inflammatory actions.

    In addition to those endogenously formed, AGEs are abundant in exogenous sources such as foods,
    especially when prepared under elevated temperatures. After ingestion, 10% of preformed AGEs are
    absorbed into the human or rodent circulation, of which two-thirds are retained in tissues. Among
    them are tissue-reactive, ß-dicarbonyl-containing intermediate products, such as methylglyoxal (MG),
    and terminal products, such as N-carboxymethyllysine (CML). MG, which has been linked to cellular
    oxidant stress and apoptosis, and CML, which is formed by glycoxidation as well as by lipoxidation,
    have both been identified in vivo and are linked to tissue toxicity. The enhanced chemical
    modification of proteins and lipids or "carbonyl stress" leads to oxidant stress and tissue damage,
    illustrating their role in the pathogenesis of diabetic complications. Other conditions, such as
    renal insufficiency, dyslipidemia, and aging are also associated with increased serum AGE levels.

    Among the multiple targets of bioactive AGEs are such diverse tissues as the vascular endothelium
    and the pancreatic islet. Pharmacological inhibition of glycoxidation protects against damage to
    either tissue." http://diabetes.diabetesjournals.org/cgi/content/full/51/7/2082

    At this point much of the research on this subject has been in mice. There are a lot of references
    cited in this article as well as a number citing this article.

    The following is for humans, but not diabetics. I can't see why the results would not apply, perhaps
    with different percentages for similar diets in diabetics.

    I would suppose that the test like HbA1c do not measure the AGE, i.e., N-carboxymethyl-lysine (CML)
    and methylglyoxal-derivatives (MG), that are in the blood serum.

    "Diet-derived AGE are major contributors to the total body AGE pool. It was postulated that a
    reduction in dietary AGE intake might impact on the high circulating AGE levels in renal failure
    patients. Twenty-six nondiabetic renal failure patients on maintenance peritoneal dialysis were
    randomized to either a high or a low AGE diet for 4 wk. Three-day dietary records, fasting blood,
    24-h urine, and dialysis fluid collections were obtained at baseline and end of study. AGE levels
    were determined ... for N-carboxymethyl-lysine (CML) and methylglyoxal-derivatives (MG). ... Low
    dietary AGE intake decreased serum CML (34%), serum MG (35%), CML-LDL (28%), CML-apoB (), dialysate
    CML (39%), and dialysate MG output (40%). High dietary AGE intake increased serum CML (29%), serum
    MG (26%), CML-LDL (50%), CML-apoB (67%), and dialysate CML output (27%). Serum AGE correlated with
    BUN ... , serum creatinine ... , total protein ... , albumin ... , and phosphorus ... . It is
    concluded that dietary glycotoxins contribute significantly to the elevated AGE levels in renal
    failure patients. Moreover, dietary restriction of AGE is an effective and feasible method to reduce
    excess toxic AGE and possibly cardiovascular associated mortality." Source: Restriction of Dietary
    Glycotoxins Reduces Excessive Advanced Glycation End Products in Renal Failure Patients
    http://www.jasn.org/cgi/content/abstract/14/3/728

    So how much do the dietary AGEs contribute to the onset of T2 DM? They certainly contribute to aging
    in general and particularly for cells/tissues (collagen) that have a long life.

    Frank
     
  10. Frank Roy

    Frank Roy Guest

    Frank Roy wrote: (a continuation of my previous post)
    > Much of this research has involved Helen Vlassara.

    > So how much do the dietary AGEs contribute to the onset of T2 DM? They certainly contribute to
    > aging in general and particularly for cells/tissues (collagen) that have a long life.
    >
    The following study there is a table showing various foods tested: Table 2. Relative concentrations
    of CML and MG derivatives in foods correlate with AGE bioreactive properties
    http://www.pnas.org/cgi/content/full/99/24/15596/T2

    "The current study demonstrates that circulating glycotoxins (sAGE) can be modulated in human
    diabetes by altering dietary AGE intake. sAGE changes are followed by parallel changes in levels of
    inflammatory molecules (CRP, TNF, and VCAM-1), all three of which are established markers of
    diabetes and vascular disease. These American Heart Association- and American Diabetic
    Association-approved diets were not enriched in fat or carbohydrate (as are Western diets) and were
    balanced for vitamin content including antioxidant supplements (25). ... Herein, glucose and lipid
    abnormalities were unremarkable over the course of the studies. The findings therefore were
    independent of dietary fat or carbohydrate and pointed to other factors, namely exogenously supplied
    dietary AGEs. Changes in CRP are found to mirror sAGE, corresponding to dietary intake, indicating
    that exogenous oxidant stress-promoting AGEs may contribute to the diabetes-related inflammatory
    state (23, 38, 39). CRP exhibits a significant association with diabetes and related vascular
    mortality (40-43). Thus, it is conceivable that the frequent intake of dietary AGE promotes a
    sustained low-grade inflammatory state. In this sense, other markers of immune response such as
    cytokines and adhesion molecules are inducible by AGEs via reactive oxygen species production and
    nuclear factor B activation (7-14, 44), properties which are also exhibited by dietary AGEs (25).
    These reactive molecules (ranging between 12 and 22 million AGE units in a "healthy meal"), which
    are "seeding" the systemic circulation regularly, could, together with hyperglycemia, contribute to
    the subtle inflammatory state associated with diabetes (23, 41-43, 45). ... The identity of
    pathogenic AGEs remains largely undefined. However, an interesting correlation between postprandial
    hyperglycemia and serum levels of MG and 3-deoxyglucosone
    (46) or a transient increase in the production of reactive oxygen species after a meal in diabetic
    subjects have been reported (47). In this study, postprandial AGE levels correspond to the
    amount of AGEs ingested (26, 27). Furthermore, the steady-state AGE levels follow a pattern
    that is consistent with the amount ingested and moves synchronously with the inflammatory
    mediators. These data may provide a further link between sustained tissue vulnerability and
    vascular dysfunction (42, 43, 45, 48-50), lasting well beyond the window of postprandial
    glycemia or lipidemia. " Source: Inflammatory mediators are induced by dietary glycotoxins, a
    major risk factor for diabetic angiopathy - http://www.pnas.org/cgi/content/full/99/24/15596
     
  11. Mike V

    Mike V Guest

    "Quentin Grady" <[email protected]> wrote in message
    news:[email protected]...
    >
    > G'day G'day Folks,
    >
    > Some posters might find the following document useful.
    >
    > http://www.eje.org/eje/149/0099/1490099.pdf
    >
    > Best wishes,
    >
    > --
    > Quentin Grady ^ ^ / New Zealand, >#,#< [ / \ /\ "... and the blind dog was leading."
    >
    > http://homepages.paradise.net.nz/quentin

    Here are some articles from Mass General Hospital which may be of interest.

    MikeV

    http://www.massgeneral.org/diabetes/type1research.htm
    http://www.massgeneral.org/diabetes/type2esearch.htm
     
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