1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...

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