Studies showed that resveratrol increased life span in lower organisms by
activating the NAD (+)-dependent histone deacetylase Sirt1. And, it was
found that that resveratrol promoted longevity and improved glucose
homeostasis in mice by stimulating the Sirt1-mediated deacetylation of the
transcriptional coactivator PGC-1alpha. [7] Researchers are interested to
know if resveratrol benefits animals suffered from chronic diseases, such as
diabetes. The following is a summary of a few interesting research studies
about the potential benefits of resveratrol on chronic diseases, such as
diabetes.

In 2001, Naderali EK and co-workers from University of Liverpool found
resveratrol (5-35 micromol/l) induced concentration-dependent relaxation of
mesenteric arteries preconstricted with noradrenaline (8 micromol/l) or KCl
(125 mmol/l) from both lean and dietary-obese rats. [1]

Hyperglycemia, a symptom of diabetes mellitus, induces hyperosmotic
responses, including apoptosis, in vascular endothelial cells and leukocytes.
Hyperosmotic shock elicits a stress response in mammalian cells, often
leading to apoptotic cell death. Moreover, resveratrol was found to
attenuate high glucose-induced apoptotic changes by virtue of its
antioxidant property. [2]

Diabetic nephropathy is a serious vascular complication and one of the
main causes of end-stage renal disease. Increased oxidative stress plays
an important role in the etiology of diabetic nephropathy. In a study,
researchers found treatment with resveratrol significantly attenuated renal
dysfunction and oxidative stress in diabetic rats. [3]

Most of type 2 diabetes mellitus patients eventually become insulin
dependent because insulin secretion by the islets of Langerhans becomes
exhausted. In the present study, researchers from Chang Gung University,
Taiwan, showed that resveratrol (3,5,4'-trihydroxylstilbene) possesses
hypoglycemic and hypolipidemic effects in streptozotocin-induced diabetes
rats. In resveratrol-treated diabetic rats, the plasma glucose concentration
on day 14 was reduced by 25.3%, and the triglyceride concentration was
reduced by 50.2% compared with the placebo-treated rats. In
nicotinamide-treated diabetic rats, the plasma glucose oncentration on day
14 was reduced only by 20.3 %, and the triglyceride concentration was
reduced by 33 %. Resveratrol administration ameliorates common DM
symptoms, such as body weight loss, polyphagia, and polydipsia. In
STZ-nicotinamide DM rats, resveratrol administration significantly decreased
insulin secretion and delayed the onset of insulin resistance. [4]

Usually, diabetic rats exhibited a significant thermal hyperalgesia and cold
allodynia along with increased plasma glucose and decreased body
weights. Allodynia means other pain. It is a painful response to a usually
non-painful stimulus. Hyperalgesia is an increased sensitivity to pain, which
may be caused by damage to nociceptors or peripheral nerves. [Wikipedia]
Sharma S and co-workers from Panjab University, India, reported treatment
with resveratrol (10mg/kg orally) from week 4 to week 6 significantly
attenuated the cold allodynia and thermal hyperalgesia, suggesting the
application of resveratrol in diabetes, especially for diabetic neuropathy. [5]

Researchers, at Boston University Medical Center, revealed inactivation of
hepatic AMP-activated protein kinase was a key event in the pathogenesis
of hyperlipidemia in diabetes (based on a study of in type 1 diabetic LDL
receptor-deficient mice). They showed that resveratrol could lower lipid
levels by activating AMP-activated protein kinase. It was about 200 times the
potency of Metformin! [6]

Recent Research Studies of Resveratrol on Diabetes

Schmatz R and co-workers from Universidade Federal de Santa Maria,
Brazil, found that treatment with resveratrol prevented the increase in
acetylcholinesterase activity and consequently memory impairment in
diabetic rats. [8]

Palsamy P and other India researchers found daily oral treatment of
resveratrol to diabetic rats for 30 days demonstrated a significant decline in
blood glucose and glycosylated hemoglobin levels and a significant
increase in plasma insulin level. The administration of resveratrol also
reverted the altered activities of the key enzymes of carbohydrate
metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase,
glucose-6-phosphatase, fructose-1,6-bisphosphatase,
glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen
phosphorylase in liver and kidney tissues of diabetic rats to near normal
levels. [9]

Researchers from New York Medical College observed that resveratrol
increased mitochondrial mass and mtDNA content, up-regulated protein
expression of electron transport chain constituents and induced
mitochondrial biogenesis factors (PGC-1alpha, Nrf-1, Tfam) in cultured
human coronary arterial endothelial cells. They found resveratrol treatment
normalized impaired mitochondrial biogenesis in aortas of type 2 diabetic
mice. This suggests the potential benefits of resveratrol on diabetes or
metabolic diseases. [10]

Researchers from Dortmund University of Technology, Germany, observed
that resveratrol could inhibit the formation of islet amyloid polypeptide
(IAPP) fibril. Following preferential partitioning of IAPP into the fluid lipid
phase, the membrane of beta-cells suffered irreversible damage and
predominantly circularly-shaped lipid-containing IAPP amyloid was formed.
Deposition of amyloid in the extracellular matrix of beta-cells commonly
occurs in type II diabetes mellitus. Thus, resveratrol may benefit animals
suffered from diabetes. [11]

Rodella LF and co-workers from University of Brescia, Italy, found
resveratrol and cobalt protoporphyrin administration increased heme
oxygenase-1 protein expression and heme oxygenase activity in the aorta
and significantly increased serum adiponectin levels, compared to untreated
diabetic rats. Increased heme oxygenase-1 expression usually improves
vascular function. [12]

Resveratrol decreased blood glucose, glycosylated hemoglobin, blood urea,
serum uric acid, serum creatinine and diminished activities of
pathophysiological enzymes such as aspartate transaminase (AST), alanine
transaminase (ALT) and alkaline phosphatase (ALP) in diabetic rats after
30 days of treatment. [13]

The prevalence of nonalcoholic fatty liver disease is high.nonalcoholic fatty
liver disease is linked to obesity, diabetes mellitus, and hypertriglyceridemia.
Approximately 20% of patients with nonalcoholic fatty liver disease will
eventually develop cirrhosis. Resveratrol was found to decrease
nonalcoholic fatty liver disease severity in rats. This effect was mediated, at
least in part, by tumor necrosis factor alpha (TNF-alpha) inhibition and
antioxidant activities. [14]

  
Resveratrol Benefits and Side Effects
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Reference:
[1] Naderali EK, Smith SL, Doyle PJ, Williams G. The mechanism of resveratrol-induced vasorelaxation differs in the mesenteric resistance
arteries of lean and obese rats. Clin Sci (Lond). 2001 Jan;100(1):55-60. [2] Chan WH. Effect of resveratrol on high glucose-induced stress in
human leukemia K562 cells. J Cell Biochem. 2005 Apr 15;94(6):1267-79. [3] Sharma S, Anjaneyulu M, Kulkarni SK, Chopra K. Resveratrol, a
polyphenolic phytoalexin, attenuates diabetic nephropathy in rats. Pharmacology. 2006;76(2):69-75. Epub 2005 Nov 11. [4] Su HC, Hung LM,
Chen JK. Resveratrol, a red wine antioxidant, possesses an insulin-like effect in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol
Metab. 2006 Jun;290(6):E1339-46. Epub 2006 Jan 24. [5] Sharma S, Kulkarni SK, Chopra K. Resveratrol, a polyphenolic phytoalexin attenuates
thermal hyperalgesia and cold allodynia in STZ-induced diabetic rats. Indian J Exp Biol. 2006 Jul;44(7):566-9. [6] Zang M, Xu S,
Maitland-Toolan KA, Zuccollo A, Hou X, Jiang B, Wierzbicki M, Verbeuren TJ, Cohen RA. Polyphenols stimulate AMP-activated protein kinase,
lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice. Diabetes. 2006 Aug;55(8):2180-91. [7] Koo SH,
Montminy M. In vino veritas: a tale of two sirt1s? Cell. 2006 Dec 15;127(6):1109-22. [8] Schmatz R, Mazzanti CM, Spanevello R, Stefanello N,
Gutierres J, Corrêa M, da Rosa MM, Rubin MA, Chitolina Schetinger MR, Morsch VM. Resveratrol prevents memory deficits and the increase
in acetylcholinesterase activity in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2009 May 21;610(1-3):42-8. Epub 2009 Mar 19. [9]
Palsamy P, Subramanian S. Modulatory effects of resveratrol on attenuating the key enzymes activities of carbohydrate metabolism in
streptozotocin-nicotinamide-induced diabetic rats. Chem Biol Interact. 2009 May 15;179(2-3):356-62. Epub 2008 Nov 19. [10] Csiszar A,
Labinskyy N, Pinto JT, Ballabh P, Zhang H, Losonczy G, Pearson KJ, de Cabo R, Pacher P, Zhang C, Ungvari ZI. Resveratrol induces
mitochondrial biogenesis in endothelial cells. Am J Physiol Heart Circ Physiol. 2009 May 8. [11] Radovan D, Opitz N, Winter R. Fluorescence
microscopy studies on islet amyloid polypeptide fibrillation at heterogeneous and cellular membrane interfaces and its inhibition by resveratrol.
FEBS Lett. 2009 May 6;583(9):1439-45. Epub 2009 Apr 2. [12] Rodella LF, Vanella L, Peterson SJ, Drummond G, Rezzani R, Falck JR,
Abraham NG. Heme oxygenase-derived carbon monoxide restores vascular function in type 1 diabetes. Drug Metab Lett. 2008
Dec;2(4):290-300. [13] Palsamy P, Subramanian S. Resveratrol, a natural phytoalexin, normalizes hyperglycemia in
streptozotocin-nicotinamide induced experimental diabetic rats. Biomed Pharmacother. 2008 Nov;62(9):598-605. Epub 2008 Jul 9. [14] Bujanda
L, Hijona E, Larzabal M, Beraza M, Aldazabal P, García-Urkia N, Sarasqueta C, Cosme A, Irastorza B, González A, Arenas JI Jr. Resveratrol
inhibits nonalcoholic fatty liver disease in rats. BMC Gastroenterol. 2008 Sep 9;8:40.
RESVERATROL Diabetes