Changes in contractile and signaling proteins in gastric antrum smooth muscle from lepob/ob mice

Abstract

The protein hormone leptin plays a key role in food intake, energy expenditure, and body weight. Leptin-deficient lepob/ob mice are an animal model of type 2 diabetes, developing obesity, hyperinsulinemia, and hyperglycemia. Approximately 30% of patients with type 2 diabetes develop gastroparesis or delayed gastric emptying. Lepob/ob mice also develop gastroparesis. The causes of diabetic gastroparesis are likely to be multifactorial, although antral hypomotility is implicated in most cases. In this study, we used western blotting to compare expression levels of contractile and signaling proteins in antrum smooth muscles from lepob/ob and control C57 mice at the ages of 7, 12, and 20 weeks. Actin levels are similar in both groups and do not change with age. IGF-1R levels are similar and decreased with age in both groups. Smooth muscle myosin heavy chain levels decreased with age in lepob/ob but not in C57 mice. Akt levels are similar in both groups at 7 and 20 weeks, but are decreased in 12 week old lepob/ob mice. pAkt levels decline with age in C57 mice, but are low in lepob/ob mice at all ages. HDAC4, γCaMKII, IκBα, and GAPDH levels are similar in both groups at 7 and 20 weeks, and all are increased in both groups at 12 weeks. Altered IGF-1 signaling and pAkt levels may be connected to the decrease in smooth muscle myosin heavy chain levels in antrum smooth muscles from lepob/ob mice. This study was supported by NIH grant RR018751.