Key points Most people find physical activity improves their feelings of wellness and vitality. Wistar rats were divided in to two groups: 1) Mild Diabetes (STZ) – received streptozotocin (glycemia from 120 to 300 mg/dL), 2) Control – received vehicle (glycemia below 120 mg/dL). During the fast, plasma glucose fell significantly in the lean (4.9 +/- 0.2 to 3.9 +/- 0.2 mmol/L), obese (5.1 +/- 0.1 to 4.2 +/- 0.2 mmol/L), and diabetic (14.7 +/- 0.7 to 10.3 +/- 1.0 mmol/L) subjects. Compared with the fasting value, the mean glycogen synthase activity assayed at low glucose-6-phosphate (G6P) concentration (active glycogen synthase) showed no significant changes during insulin infusion before glyburide treatment. It is generally assumed that ketosis occurs in diabetes only after liver glycogen is exhausted. Treatment of HepG2 cells with 1 nm melatonin markedly increased glycogen synthesis which was blocked by the melatonin receptor antagonist luzindole. Recent studies have demonstrated that oxidative stress, resulting from enhanced exposure to oxidants, causes impaired insulin signaling and insulin resistance of skeletal muscle glucose transport, in part due to reduced suppression of GSK-3 activity and increased IRS-1 Ser(307) phosphorylation.
We further developed a structure-activity relationship for the inhibition of glycogen phosphorylase-a. Though promising, this model still does not completely explain the molecular basis for the insulin-mediated activation of glycogen synthase, which remains one of the many unknowns of insulin action.