Pathogenesis of Type 2 Diabetes

The results of these studies showed a remarkable similarity in the effects produced by the selective DPP-8 inhibitor and a//o-isoleucyl thiazolidide [21]. Both compounds produced mortality and alopecia at the highest doses tested, and both also produced thrombocytopenia of similar magnitude at doses 30mpk, and enlarged spleens and lymph nodes at all doses tested. The QPP selective inhibitor produced significant reductions in reticulocyte counts at the 100 mpk dose. No other changes were noted. In contrast to the above compounds, 

During the course of these studies, another proline selective peptidase, DPP-9, closely related to DPP-8, was described [22], The DPP-8 selective inhibitor was then found to be a dual DPP-8/9 inhibitor. Thus inhibition of one or both of these enzymes, or possibly another closely related enzyme, may be responsible for the observed toxicity. Efforts to identify potent and selective inhibitors of the individual enzymes in order to further deduce the mechanism of toxicity have thus far not succeeded. 

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Withers DJ, White M (2000) Perspective the insulin signaling system - a common link in the pathogenesis of type 2 diabetes. Endocrinology 141 1917-1921... 

Bays, H., Mandarino, L., and DeEronzo, R. A. (2004). Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus Peroxisomal proleferator-activated receptor agonists provide a rational therapeutic approach. /. Clin. Endocrinol. Metab. 89, 463 78. 

Baudry A, Leroux L, Jackerott M, Joshi RL. Genetic manipulation of msuiin signaling, action and secretion in mice. Insights into glucose homeostasis and pathogenesis of type 2 diabetes. EMBO reports 2002 3 323-8. 

DeEronzo RA. Pathogenesis of type 2 diabetes mellitus Metabolic and molecular implications for identifying diabetes genes. Diabetes 1997 5 117-269. 

Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 1999 104(6) 787-794. 

Improvement in the insuhn resistance that under-hes the pathogenesis of type 2 diabetes and the metabolic syndrome leads to pleiotropic effects, including reduced glycemia, enhanced beta cell function, reduction in the inflammatory milieu, improvement in dyshpidemia and blood pressure vascular endothehal function, cardiovascular risk reduction, and in the prevention of diabetes. 

Nanck MA, Bailer B, Meier JJ. Gastric inhibitory polypeptide and glncagon-like peptide-1 in the pathogenesis of type 2 diabetes. Diabetes 2004 53(Snppl. 3) S190-6. 

Boden, G, Pathogenesis of type 2 diabetes. Insulin resistance, Endocrinol Metab Clin North Am, 2001. 30(4) 801-815, v. 

Akash MS, Rehman K, Chen S (2013) Role of inflammatory mechanisms in pathogenesis of type 2 diabetes melhtus. J Cell Biochem 114, 525-31. 

The lipotoxicity hypothesis indicates that fat-induced hepatic insulin resistance (FIHIR) may play a major role in the pathogenesis of type 2 diabetes, the most common form of diabetes mellitus. It has been suggested that berberine exerts a therapeutic effect on FlHlR in a model of type 2 diabetes in hamsters by modulating the hepatic SREBPs, LXRa, and PPARa transcriptional programs [30]. 

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