Tumor necrosis factor alpha and insulin resistance in obese type 2 diabetic patients.

The relationship between basal serum tumor necrosis factor alpha (TNFalpha) levels and peripheral tissue (muscle) sensitivity to insulin was examined in 63 subjects with normal glucose tolerance (NGT), 18 subjects with impaired glucose tolerance (IGT), and 123 patients with type 2 diabetes mellitus (T2DM). The BMI was similar in NGT (28.8+/-0.

Physiological hyperinsulinemia impairs insulin-stimulated glycogen synthase activity and glycogen synthesis.

Although chronic hyperinsulinemia has been shown to induce insulin resistance, the basic cellular mechanisms responsible for this phenomenon are unknown. The present study was performed 1) to determine the time-related effect of physiological hyperinsulinemia on glycogen synthase (GS) activity, hexokinase II (HKII) activity and mRNA content, and GLUT-4 protein in muscle from healthy subjects, and 2) to relate hyperinsulinemia-induced alterations in these parameters to changes in glucose metabolism in vivo. Twenty healthy subjects had a 240-min euglycemic insulin clamp study with muscle biopsies and then received a low-dose insulin infusion for 24 (n = 6) or 72 h (n = 14) (plasma insulin concentration = 121 +/- 9 or 143 +/- 25 pmol/l, respectively).

Bromocriptine: a novel approach to the treatment of type 2 diabetes.

Objective: In vertebrates, body fat stores and insulin action are controlled by the temporal interaction of circadian neuroendocrine oscillations. Bromocriptine modulates neurotransmitter action in the brain and has been shown to improve glucose tolerance and insulin resistance in animal models of obesity and diabetes. We studied the effect of a quick-release bromocriptine formulation on glucose homeostasis and insulin sensitivity in obese type 2 diabetic subjects.

Insulin-induced hexokinase II expression is reduced in obesity and NIDDM.

NIDDM and obesity are characterized by decreased insulin-stimulated glucose uptake in muscle. It has been suggested that impaired glucose phosphorylation to glucose-6-phosphate, catalyzed in muscle by hexokinase (HK)II, may contribute to this insulin resistance. Insulin is known to increase HKII mRNA, protein, and activity in lean nondiabetic individuals.

Effects of insulin on subcellular localization of hexokinase II in human skeletal muscle in vivo.

The phosphorylation of glucose to glucose-6-phosphate, catalyzed by hexokinase, is the first committed step in glucose uptake into skeletal muscle. Two isoforms of hexokinase, HKI and HKII, are expressed in human skeletal muscle, but only HKII expression is regulated by insulin. HKII messenger RNA, protein, and activity are increased after 4 h of insulin infusion; however, glucose uptake is stimulated much more rapidly, occurring within minutes.