scholarly journals Protective effect of testosterone on early apoptotic damage induced by streptozotocin in rat pancreas

2005 ◽  
Vol 187 (2) ◽  
pp. 217-224 ◽  
Author(s):  
S Morimoto ◽  
C A Mendoza-Rodríguez ◽  
M Hiriart ◽  
M E Larrieta ◽  
P Vital ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Protective Effect ◽  
Insulin Dependent Diabetes Mellitus ◽  
Pancreatic Tissue ◽  
Dependent Diabetes Mellitus ◽  
Beta Cell Apoptosis ◽  
Β Cells ◽  
Citrate Buffer ◽  
Rat Pancreas ◽  
Apoptotic Damage

Beta-cell apoptosis is responsible for the development of insulin-dependent diabetes mellitus in the streptozotocin (STZ) rat model. It has been demonstrated that steroid hormones possess antioxidant and protective antiapoptotic effects in many tissues. The aim of the present study was to investigate the early apoptotic damage induced by STZ in rat pancreas, and the effect of testosterone in preventing apoptosis of pancreatic β cells. Intact and castrated adult male Wistar rats were subjected to a unique injection of STZ 60 mg/kg (body weight) in citrate buffer, and the kinetics of apoptosis in β cells was assessed. Insulin and glucose were measured by RIA and a glucometer respectively, and in pancreatic tissue by immunohistochemistry. At 6 h after STZ injection, a marked increase in apoptotic β cells was detected; however, glucose and insulin serum levels were not significantly different from the controls. The castrated animals presented higher percentages of apoptotic β cells (65.75 ± 5.42%) than intact males (20.6 ± 4.38%) and castrated, testosterone-substituted males (30.66 ± 1.38%). The decrease in apoptotic β cells induced by testosterone was reversed by the antiandrogen flutamide (67.69 ± 3.45%). The overall results indicate that early apoptotic damage produced by STZ in castrated animals was reversed by testosterone, suggesting that this hormone exerts a natural protective effect in rat pancreas. This effect could help to explain some sexual differences in diabetes mellitus incidence in man, reinforcing the idea that new approaches in steroid hormone therapies should be considered for treatment of this disease.

scholarly journals Granulomatous Pancreatitis in a Patient with Acute Manifested Insulin-Dependent Diabetes Mellitus

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Václav Mandys ◽  
Michal Kheck ◽  
Michal Anděl
Keyword(s):  
Diabetes Mellitus ◽  
Human Population ◽  
Rare Condition ◽  
Insulin Dependent Diabetes Mellitus ◽  
Epithelioid Cell ◽  
Pancreatic Tissue ◽  
Postmortem Examination ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent

Isolated granulomatous noncaseating pancreatitis is a rare condition exceptionally described in human population. We demonstrate a case of the a 71-years-old female patient suffering from recent diabetes mellitus, generalized atherosclerosis and hypertension who died due to pulmonary embolism and terminal bronchopneumonia. Lipomatosis of pancreatic tissue was observed during the postmortem examination. Histological examination of pancreatic tissue discovered multiple small noncaseating epithelioid cell and giant cell granulomas, partly replacing the islets of Langerhans. To our knowledge, our case represents the first description of noninfectious granulomatous pancreatitis associated with acute manifested insulin-dependent diabetes mellitus.

Epac2: a sulfonylurea receptor?

2012 ◽  
Vol 40 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Holger Rehmann
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Critical Discussion ◽  
Dependent Diabetes Mellitus ◽  
Sulfonylurea Receptor ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
K Channels ◽  
Glucose Levels ◽  
Voltage Dependent

Sulfonylureas are widely used oral drugs in the treatment of diabetes mellitus. They function by the inhibition of ATP-sensitive K+ channels in pancreatic β-cells, which are thus considered the ‘classical’ sulfonylurea receptor. Next to the ATP-sensitive K+ channels, additional sulfonylurea-interacting proteins were identified, which might contribute to the physiological effects of this drug family. Most recently, Epac2 (exchange protein directly activated by cAMP 2) was added to the list of sulfonylurea receptors. However, this finding caused controversy in the literature. The critical discussion of the present paper comes to the conclusion that sulfonylureas are not able to activate Epac2 directly and are unlikely to bind to Epac2. Increased blood glucose levels after food intake result in the secretion of insulin from pancreatic β-cells. Glucose levels are detected ‘indirectly’ by β-cells: owing to increased glycolysis rates, the ratio of cellular ATP/ADP increases and causes the closure of ATP-sensitive K+ channels. In consequence, cells depolarize and voltage-dependent Ca2+ channels open to cause an increase in the cellular Ca2+ concentration. Finally, Ca2+ induces the fusion of insulin-containing granules with the plasma membrane. Sulfonylureas, such as tolbutamide, glibenclamide or acetohexamide, form a class of orally applicable drugs used in the treatment of non-insulin-dependent diabetes mellitus.

Relationships among residual β cells, exocrine pancreas, and islet cell antibodies in insulin-dependent diabetes mellitus

Metabolism ◽  
1993 ◽  
Vol 42 (2) ◽  
pp. 196-203 ◽  
Author(s):  
Koji Nakanishi ◽  
Tetsuro Kobayashi ◽  
Hikari Miyashita ◽  
Minoru Okubo ◽  
Tadao Sugimoto ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Exocrine Pancreas ◽  
Islet Cell ◽  
Islet Cell Antibodies ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Β Cells ◽  
Insulin Dependent

scholarly journals Islet Amyloid Polypeptide: A Review of Its Biology and Potential Roles in the Pathogenesis of Diabetes Mellitus

1993 ◽  
Vol 30 (4) ◽  
pp. 317-332 ◽  
Author(s):  
T. D. O'Brien ◽  
P. C. Butler ◽  
P. Westermark ◽  
K. H. Johnson
Keyword(s):  
Diabetes Mellitus ◽  
Islet Amyloid Polypeptide ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Molar Ratio ◽  
Dependent Diabetes Mellitus ◽  
Human Beings ◽  
Β Cells ◽  
Islet Amyloid ◽  
Insulin Dependent

Islet amyloidosis (IA) is the principal lesion in the endocrine pancreas of human beings with non-insulin-dependent diabetes mellitus (NIDDM) and in the similar forms of diabetes mellitus in domestic cats and macaques. As such, the delineation of the pathogenesis of this form of amyloidosis may be crucial to the understanding of the development and progression of NIDDM. Islet amyloid polypeptide (IAPP) is a recently discovered polypeptide that is the principal constituent of IA in human beings, cats, and macaques. IAPP is produced by the pancreatic β-cells and is co-packaged with insulin in the β-cell secretory vesicles. Immunohistochemical and physiologic evidence supports the notion that the β-cells are heterogenous with respect to their relative contents of insulin and IAPP. Therefore, although IAPP is co-secreted with insulin in response to a variety of well-known insulin secretogogues, the molar ratio of these two proteins that is released from the islets may vary, depending upon the glucose concentration and prevailing metabolic milieu. IAPP is highly conserved among mammalian species and has about 45% homology to another neuropeptide, calcitonin gene-related peptide. IAPP is encoded by a single-copy gene located, in the human being, on chromosome 12. IAPP is expressed as a 93 (murine)–89 (human)-amino acid prepropolypeptide that is processed enzymatically, resulting in the removal of amino- and carboxy-terminal propeptide segments. The 20–29 region of the IAPP molecule is most important in the ability of IAPP to form amyloid fibrils. The role of IAPP and IA in the pathogenesis of human NIDDM and similar forms of diabetes mellitus in cats and macaques may involve several possible mechanisms, including 1) direct physical/chemical damage to β-cells, resulting in necrosis and loss of functional islet tissue, 2) biologic activities of IAPP that oppose those of insulin or abnormally suppress insulin secretion, and 3) interference by IA deposits of passage of insulin out of β-cells and/or entrance of glucose and other secretogogues into the islet. The roles of each of these possible mechanisms have yet to be demonstrated. In addition, the physiological significance of the apparent IAPP deficiency in both insulin-dependent diabetes mellitus and NIDDM is currently unknown.

scholarly journals Nitric Oxide Primes Pancreatic β Cells for Fas-mediated Destruction in Insulin-dependent Diabetes Mellitus

1997 ◽  
Vol 186 (8) ◽  
pp. 1193-1200 ◽  
Author(s):  
Giorgio Stassi ◽  
Ruggero De Maria ◽  
Giuliana Trucco ◽  
William Rudert ◽  
Roberto Testi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Fas Ligand ◽  
Cell Damage ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Insulin Dependent

Fas is an apoptosis-inducing surface receptor involved in controlling tissue homeostasis and function at multiple sites. Here we show that β cells from the pancreata of newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients express Fas and show extensive apoptosis among those cells located in proximity to Fas ligand–expressing T lymphocytes infiltrating the IDDM islets. Normal human pancreatic β cells that do not constitutively express Fas, become strongly Fas positive after interleuken (IL)-1β exposure, and are then susceptible to Fas-mediated apoptosis. NG-monomethyl-l-arginine, an inhibitor of nitric oxide (NO) synthase, prevents IL-1β–induced Fas expression, whereas the NO donors sodium nitroprusside and nitric oxide releasing compound (NOC)-18, induce functional Fas expression in normal pancreatic β cells. These findings suggest that NO-mediated upregulation of Fas contributes to pancreatic β cell damage in IDDM.

scholarly journals Protection against lipoapoptosis of β cells through leptin-dependent maintenance of Bcl-2 expression

1998 ◽  
Vol 95 (16) ◽  
pp. 9558-9561 ◽  
Author(s):  
Michio Shimabukuro ◽  
May-Yun Wang ◽  
Yan-Ting Zhou ◽  
Christopher B. Newgard ◽  
Roger H. Unger
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Fatty Acyl ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Β Cells ◽  
Leptin Receptors ◽  
Triacsin C ◽  
Insulin Dependent ◽  
Induced Apoptosis

Obesity causes its complications through functional and morphologic damage to remotely situated tissues via undetermined mechanisms. In one rodent model of obesity, the Zucker diabetic fatty fa/fa rat, overaccumulation of triglycerides in the pancreatic islets may be responsible for a gradual depletion of β cells, leading to the most common complication of obesity, non-insulin-dependent diabetes mellitus. At the onset of non-insulin-dependent diabetes mellitus, the islets from fa/fa rats contain up to 100 times the fat content of islets from normal lean rats. Ultimately, about 75% of the β cells disappear from these fat-laden islets as a consequence of apoptosis induced by long-chain fatty acids (FA). Here we quantify Bcl-2, the anti-apoptosis factor in these islets, and find that Bcl-2 mRNA and protein are, respectively, 85% and 70% below controls. In normal islets cultured in 1 mM FA, Bcl-2 mRNA declined by 68% and completely disappeared in fa/fa islets cultured in FA. In both groups, suppression was completely blocked by the fatty acyl-CoA synthetase inhibitor, triacsin C, evidence of its mediation by fatty acyl-CoA. To determine whether leptin action blocked FA-induced apoptosis, we cultured normal and fa/fa islets in 1 mM FA with or without leptin. Leptin completely blocked FA-induced Bcl-2 suppression in normal islets but had no effect on islets from fa/fa rats, which are unresponsive to leptin because of a mutation in their leptin receptors (OB-R). However, when wild-type OB-R is overexpressed in fa/fa islets, leptin completely prevented FA-induced Bcl-2 suppression and DNA fragmentation.

Protective effect of taurine on rats with experimental insulin-dependent diabetes mellitus

2008 ◽  
Vol 146 (2) ◽  
pp. 226-228 ◽  
Author(s):  
L. K. Gavrovskaya ◽  
O. V. Ryzhova ◽  
A. F. Safonova ◽  
A. K. Matveev ◽  
N. S. Sapronov
Keyword(s):  
Diabetes Mellitus ◽  
Protective Effect ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent
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