alpha-chymotrypsin and Insulin-Resistance

We investigated whether PPARγ modulates adipose tissue BCAA metabolism, and whether this mediates the attenuation of obesity-associated insulin resistance induced by pharmacological PPARγ activation.. Mice with adipocyte deletion of one or two PPARγ copies fed a chow diet and rats fed either chow, or high fat (HF) or HF supplemented with BCAA (HF/BCAA) diets treated with rosiglitazone (30 or 15 mg/kg/day, 14 days) were evaluated for glucose and BCAA homeostasis.. Adipocyte deletion of one PPARγ copy increased mice serum BCAA and reduced inguinal white (iWAT) and brown (BAT) adipose tissue BCAA incorporation into triacylglycerol, as well as mRNA levels of branched-chain aminotransferase (BCAT)2 and branched-chain α-ketoacid dehydrogenase (BCKDH) complex subunits. Adipocyte deletion of two PPARγ copies induced lipodystrophy, severe glucose intolerance and markedly increased serum BCAA. Rosiglitazone abolished the increase in serum BCAA induced by adipocyte PPARγ deletion. In rats, HF increased serum BCAA, such levels being further increased by BCAA supplementation. Rosiglitazone, independently of diet, lowered serum BCAA and upregulated iWAT and BAT BCAT and BCKDH activities. This was associated with a reduction in mTORC1-dependent inhibitory serine phosphorylation of IRS1 in skeletal muscle and whole-body insulin resistance evaluated by HOMA-IR.. PPARγ, through the regulation of both BAT and iWAT BCAA catabolism in lipoeutrophic mice and muscle insulin responsiveness and proteolysis in lipodystrophic mice, is a major determinant of circulating BCAA levels. PPARγ agonism, therefore, may improve whole-body and muscle insulin sensitivity by reducing blood BCAA, alleviating mTORC1-mediated inhibitory IRS1 phosphorylation.

Topics: Adipose Tissue, Brown; Adipose Tissue, White; Amino Acids, Branched-Chain; Animals; Chymotrypsin; Diet, High-Fat; Hypoglycemic Agents; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; PPAR gamma; Rats; Rats, Sprague-Dawley; Rosiglitazone; Triglycerides

Our previous studies showed that porcine pancreatic enzymes in Syrian golden hamsters with peripheral insulin resistance normalizes the plasma insulin level, reduces the size of enlarged islets and inhibits the increased DNA synthesis in the beta-cell of islets.. In order to exclude the possibility that these effects was attributed to some contaminants of this crude material, we tested the effect of purified fungal pancreatic enzyme (FPE) that contains primarily amylase and lipase without (FPE) and with addition of chymotrypsin (FPE+chy).. In a pilot study we tested the effect of different doses of FPE given in drinking water on insulin level, islet size and DNA synthesis of islet cells in hamsters with induced peripheral insulin resistance by a high fat diet. The most effective dose of FPE on these parameters was used in a long-term experiment with FPE and FPE+chy in hamsters fed a high-fat diet for 36 or 40 weeks.. In the pilot study a dose of 2 g/kg body weight was found to be optimal for controlling the body weight, normalizing plasma insulin level, the size of islets, the DNA synthesis and the number of insulin cells in the islets. These data were produced in the long-term study, where steatorrhea was also inhibited. Addition of chymotrypsin had no effects on these parameters.. Pancreatic lipase and amylase appear to be responsible for the observed effects and offer a safe and effective natural product for the treatment of pancreatic diseases, including acute pancreatitis, chronic pancreatic, cystic fibrosis and any conditions associated with peripheral insulin resistance, including obesity and type 2 diabetes. The possible mechanism of the action is discussed.

Topics: Amylases; Animals; Cell Count; Chymotrypsin; Cricetinae; Diabetes Mellitus, Type 2; Diet, High-Fat; DNA; Dose-Response Relationship, Drug; Female; Fungal Proteins; Fungi; Insulin; Insulin Resistance; Islets of Langerhans; Lipase; Mesocricetus; Obesity; Organ Size; Pilot Projects; Time Factors

Topics: Adolescent; Adult; Aged; Animals; Blood Glucose; Blood Proteins; Chymotrypsin; Diabetes Mellitus; Diaphragm; Endopeptidases; Female; Glycosuria; Humans; Immune Sera; In Vitro Techniques; Injections, Intramuscular; Injections, Intravenous; Insulin; Insulin Antibodies; Insulin Resistance; Male; Middle Aged; Pituitary-Adrenal Function Tests; Rats

Topics: Arabinose; Biological Transport; Carbohydrate Metabolism; Chymotrypsin; Erythrocytes; Fructose; Galactose; Glycerol; Insulin; Insulin Resistance; Lipase; Mannose; Permeability; Pharmacology; Phospholipases; Research; Ribose; Sorbose; Threonine; Urea; Valine; Xylose