Miglitol suppresses the postprandial increase in interleukin 6 and enhances active glucagon-like peptide 1 secretion in viscerally obese subjects.

Visceral obesity and insulin resistance are regarded as risk factors for atherosclerosis. Epidemiologic studies have demonstrated long-term anti-atherosclerotic effects with administration of alpha-glucosidase inhibitors. Alpha-glucosidase inhibitors also have been reported to enhance glucagon-like peptide 1 (GLP-1) secretion. We compared the postprandial effects of a single administration of miglitol and acarbose on glucose and lipid metabolism, on insulin requirement, on GLP-1 secretion, and on inflammatory and endothelial markers in viscerally obese subjects. Twenty-four viscerally obese subjects with relative insulin resistance participated in this study. Subjects were given a single dose of miglitol (50 mg), acarbose (100 mg), or placebo blindly and randomly before a meal in a crossover design. The meal loads after drug administration were tested 3 times within 2 weeks. We measured glucose, insulin, lipids, lipoprotein lipase, interleukin 6, intracellular adhesion molecule 1, vascular cell adhesion molecule 1, and active GLP-1 at before and various minutes after the meal. Single administration of both alpha-glucosidase inhibitors had several beneficial effects in improving postprandial hyperglycemia and reducing postprandial insulin requirement approximately 25% of placebo without adversely affecting lipid profiles. Although lipoprotein lipase levels within 2 hours after the meal did not show differences among miglitol, acarbose, and placebo administrations, miglitol significantly suppressed the increases in triglycerides, remnant-like particle triglycerides, and remnant-like particle cholesterol compared to acarbose and placebo in the early phase. Miglitol also significantly enhanced active GLP-1 secretion to a greater extent than acarbose (P < .01) and placebo (P < .001), and significantly suppressed the postprandial increase in interleukin 6 compared to placebo (P < .01). The results point to the potential suitability of miglitol as an anti-atherosclerotic effect in viscerally obese subjects, in preference to acarbose. Further studies are needed to elucidate the long-term effects on enhanced GLP-1 secretion and anti-atherosclerosis.

Cloning of cDNA encoding a regeneration-associated muscle protease whose expression is attenuated in cell lines derived from Duchenne muscular dystrophy patients.

In the dystrophin-mutant mdx mouse, an animal model for Duchenne muscular dystrophy (DMD), damaged skeletal muscles are efficiently regenerated and thus the animals thrive. The phenotypic differences between DMD patients and the mdx mice suggest the existence of factors that modulate the muscle wasting in the mdx mice. To identify these factors, we searched for mRNAs affected by the mdx mutation by using cDNA microarrays with newly established skeletal muscle cell lines from mdx and normal mice. We found that in the mdx muscle cell line, 12 genes, including L-arginine:glycine amidinotransferase and thymosin beta4, are up-regulated, whereas 7 genes, including selenoprotein P and a novel regeneration-associated muscle protease (RAMP), are down-regulated. Northern blot analysis and in situ hybridization revealed that RAMP mRNA is predominantly expressed in normal skeletal muscle and brain, and its production is enhanced in the regenerating area of injured skeletal muscle in mice. RAMP expression was much lower in individual muscle cell lines derived from biopsies of six DMD patients compared to a normal muscle cell line. These results suggest that RAMP may play a role in the regeneration of skeletal muscle and that its down-regulation could be involved in the progression of DMD in humans.