Beta Cell Apoptosis in NIDDM

Quentin: Beta-cell apoptosis in the pathogenesis of human type 2 diabetes mellitus

Quoted message said:

eje.org1490099.pdfOpen ↗

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
arbl.cvmbs.colostate.eduindex.htmlOpen ↗

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
pharmrev.aspetjournals.org101Open ↗

Frank

Quentin Grady <[email hidden]> wrote in message
news:<[email hidden]>...

Quoted message said:

G'day G'day Folks,

Some posters might find the following document useful.

eje.org1490099.pdfOpen ↗

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

"Frank Roy" <[email hidden]> wrote in message "]news:[email hidden]...

Quoted message said:

Quentin: Beta-cell apoptosis in the pathogenesis of human type 2 diabetes mellitus

Quoted message said:

eje.org1490099.pdfOpen ↗

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

arbl.cvmbs.colostate.eduindex.htmlOpen ↗

Quoted message said:

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 pharmrev.aspetjournals.org101Open ↗

Frank

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

MikeV

"Frank Roy" <[email hidden]> wrote in message "]news:[email hidden]...

Quoted message said:

Quentin: Beta-cell apoptosis in the pathogenesis of human type 2 diabetes mellitus

Quoted message said:

eje.org1490099.pdfOpen ↗

I had some problem getting this article uploaded. I did some

Quoted message said:

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.

"tcomeau" <[email hidden]> wrote in message
"]news:[email hidden]...

Quoted message said:

Quentin Grady <[email hidden]> wrote in message

news:<[email hidden]>...

Quoted message said:

Quoted message said:

G'day G'day Folks,

Some posters might find the following document useful.

eje.org1490099.pdfOpen ↗

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

"Quentin Grady" <[email hidden]> wrote in message
"]news:[email hidden]...

Quoted message said:

G'day G'day Folks,

Some posters might find the following document useful.

eje.org1490099.pdfOpen ↗

Best wishes,

--
Quentin Grady ^ ^ / New Zealand, >#,#< [ / \ /\ "... and the blind dog was leading."

homepages.paradise.net.nzquentinOpen ↗

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:

joplink.net200207 02.pdfOpen ↗

I posted a question on this topic and received a response from a biochemist (Orion) - below:

bbs.eatprotein.comultimatebb.cgiOpen ↗

I do not have a financial interest in the above discussion board or any of its contents. Mike

Mike V said:

Hi Quentin: Useful overview on topic. regards MikeV

We can agree on that!

Quoted message said:

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.
groups.google.comgroupsOpen ↗

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." diabetes.diabetesjournals.org2082Open ↗

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
jasn.org728Open ↗

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

Frank Roy wrote: (a continuation of my previous post)

Quoted message said:

Much of this research has involved Helen Vlassara.

Quoted message said:

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
pnas.orgT2Open ↗

"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 - pnas.org15596Open ↗

"Quentin Grady" <[email hidden]> wrote in message
"]news:[email hidden]...

Quoted message said:

G'day G'day Folks,

Some posters might find the following document useful.

eje.org1490099.pdfOpen ↗

Best wishes,

--
Quentin Grady ^ ^ / New Zealand, >#,#< [ / \ /\ "... and the blind dog was leading."

homepages.paradise.net.nzquentinOpen ↗

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

MikeV

massgeneral.orgtype1research.htmOpen ↗
massgeneral.orgtype2esearch.htmOpen ↗