1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...
1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...
1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...
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3<br />
Sitagliptin (MK-0431)<br />
Vildagliptin (LAF-237)<br />
4) Potential effects on preservation and augmentation<br />
of beta-cell mass<br />
Disclosure statement: The author has nothing to disclose.<br />
Abbreviations : AIR g , Acute insulin response to IV glucose; AGEs, advanced<br />
glycation end-products; AUC, area under a curve; CSII, continuous subcutaneous insulin<br />
infusion; DM 2, type 2 diabetes mellitus; DPP-IV, dipeptidyl peptidase –IV; ER,<br />
endoplasmic reticulum; FA, fatty acid; FFAs, free fatty acids; FSIVGTT, frequently<br />
sampled intravenous glucose tolerance test; GIP, glucose-dependent insulinotropic<br />
polypeptide; GLP-1, glucagon like peptide-1; GLP-1R, GLP-1 receptor; HOMA,<br />
homeostasis model assessment; HOMA-IR, homeostasis model assessment of insulin<br />
resistance; HOMA-β, homeostasis model assessment of beta-cell function; IAPP, islet<br />
amyloid polypeptide; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; IL,<br />
interleukin; M, insulin-stimulated glucose disposal; ROS, reactive oxygen species; TZDs,<br />
thiazolidinediones; TNF-α, tumor necrosis factor-α; UKPDS, United Kingdom Prospective<br />
Diabetes Study.<br />
I. Introduction<br />
It is well known that there is a progressive deterioration in beta-cell function over<br />
time in type 2 diabetes (DM2), as indicated by the UKPDS (United Kingdom Prospective<br />
Diabetes Study) (1,2), regardless of therapy allocation, albeit conventional (mainly diet),<br />
insulin, chlorpropamide, glibenclamide or metformin treatment. Moreover, the pancreatic<br />
islet function was found to be about 50% of normal at the time of diagnosis, independent of<br />
the degree of insulin resistance, with the reduction in function probably commencing 10-12<br />
years prior to diagnosis and aggravated by increasing fasting plasma glucose levels (3). The