PI3K{gamma} ablation does not promote diabetes in db/db mice, but improves insulin sensitivity and reduces pancreatic {beta}-cell apoptosis [Research]

PI3K has emerged as a promising target for the treatment of obesity and insulin resistance; however, previous studies have indicated that PI3K activity in pancreatic β cells is required for normal insulin secretion in response to glucose. Hence, a possible deterioration of insulin secretion capacity in patients who are predisposed to the failure of pancreatic β-cell function is a major concern for the pharmacologic inhibition of PI3K. To address this issue, we investigated the effects of PI3K ablation in db/db diabetic mice, a genetic model of obesity-driven β-cell failure and diabetes. Mice that lacked PI3K were backcrossed into db/+ mice C57BL/KS (>10 generations) to obtain db/db–PI3K–/– mice. db/db–PI3K–/– mice and control db/db mice were phenotyped for glucose homeostasis, insulin sensitivity, insulin secretion, steatosis, metabolic inflammation, pancreatic islet morphometry, islet cellular composition, and inflammation. Pancreatic β-cell apoptosis and proliferation were also evaluated. db/db–PI3K–/– mice and control db/db mice developed similar body weight, steatosis, glycemia, and insulin levels after a glucose load; however, db/db–PI3K–/– mice displayed improved insulin tolerance, higher levels of fasting serum insulin, and lower pancreatic insulin content. In db/db–PI3K–/– mice, the number of adipose tissue macrophages was similar to control, but displayed ...
Source: FASEB Journal - Category: Biology Authors: Tags: Research Source Type: research