Luminal α-glucosidase inhibition improves insulin sensitivity and modulates glycemic and lipid profiles in obese rats with type 2 diabetes mellitus

Atherogenic plasma lipid and glycemic profiles are commonly observed in obesity and adult-onset type 2 diabetes mellitus (T2DM) and may improve following therapeutic intervention. The effects of the luminal α-glucosidase inhibitor miglitol (MIG) on carbohydrate digestion and plasma lipid profiles were evaluated in adult male obese spontaneously hypertensive and diabetes-prone/Ntul//-cp rats, a genetic model that develops early-onset obesity and T2DM independently of diet. Rats were fed either a nutritionally complete diet (formulated by the United States Department of Agriculture) containing 54% sucrose as the carbohydrate component (control) or the same diet supplemented with MIG at 150 mg/kg of diet admixture ad libitum for <8 weeks. MIG treatment resulted in a ~15% decrease in energy intake (p<0.05), net weight gain (p<0.05), and a 14% decrease in adiposity (p<0.05), along with significant decreases in fasting glucose, insulin, and glycated hemoglobin (p<0.05). In addition, MIG reduced the glucose area under the curve by 20% (p<0.05), triglycerides by 15% (p<0.05), and the total cholesterol, α-lipoprotein (low-density lipoprotein), and β-lipoprotein (high-density lipoprotein) fractions by 20% (p<0.05, all comparisons). MIG regimen also led to decreases in liver glucokinase, malic enzyme, and glucose-6-phosphate dehydrogenase (p<0.05). In conclusion, these results suggest that therapeutic α-glucosidase inhibition through MIG improves multiple insulin-related atherogenic parameters and may serve as a useful adjunct in the long-term clinical management of plasma lipid and glycemic profiles in the glucose-intolerant states of obesity and T2DM.