Repurposing matrine for the treatment of hepatosteatosis and associated disorders in glucose homeostasis in mice.

The present study investigated the efficacy of the hepatoprotective drug matrine (Mtr) for its new application for hepatosteatosis and associated disorders in glucose homeostasis. The study was performed in two nutritional models of hepatosteatosis in mice with various abnormal glucose homeostasis: (1) high-fructose diet (HFru) induced hepatosteatosis and glucose intolerance from hepatic, and (2) hepatosteatosis and hyperglycemia induced by high-fat (HF) diet in combination with low doses of streptozotocin (STZ). Administration of Mtr (100 mg/kg every day in diet for 4 weeks) abolished HFru-induced hepatosteatosis and glucose intolerance. These effects were associated with the inhibition of HFru-stimulated de novo lipogenesis (DNL) without altering hepatic fatty acid oxidation. Further investigation revealed that HFru-induced endoplasmic reticulum (ER) stress was inhibited, whereas heat-shock protein 72 (an inducible chaperon protein) was increased by Mtr. In a type 2 diabetic model induced by HF-STZ, Mtr reduced hepatosteatosis and improved attenuated hyperglycemia. The hepatoprotective drug Mtr may be repurposed for the treatment of hepatosteatosis and associated disorders in glucose homeostasis. The inhibition of ER stress associated DNL and fatty acid influx appears to play an important role in these metabolic effects.

The clinical analysis of hyperglycemic controls with four times daily administration of insulin on diabetes in pregnancy / 대한산부인과학회지

OBJECTIVE: To determine whether administrating insulin four times daily, compared to 1-3 times daily, improves maternal and perinatal outcomes of diabetes. METHODS: From August 1998 to April 2004, the 14 pregnant diabetic women were treated with four times daily administration of NPH and insulin-lispro and 15 pregnant diabetic women were treated with 1-3 times daily administration of Mixtard (30% RI, 70% NPH) or NPH. We compared the maternal and fetal complications between two groups. The goals for therapy are to achieve and maintain normoglycemia (premeal whole blood capillary glucose levels of less than 90 mg/dL and 1-hour after-meal levels of less than 120 mg/dL). RESULTS: The pregnant diabetic women who were treated with four times daily administration of NPH and Insulin lispro, instead of 1-3 times daily administration of Mixtard or NPH, resulted in better maternal and fetal outcome. But there was no significant difference between two groups statistically. CONCLUSION: This study reveals that this four times daily administration of NPH and insulin-lispro protocol achieved the glucose target level without maternal hypoglycemic events and helped to reduce the perinatal complications in pregnant diabetic women.