Pathophysiological analyses of glucagon dysregulation in development of glucose intolerance and diabetes.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461336
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Osaka University
• Principal Investigator: Kawamori Dan 大阪大学, 医学系研究科, 助教 (50622362)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 糖尿病 / グルカゴン / エネルギー代謝

Outline of Final Research Achievements

At this moment, mechanisms for dysregulated glucagon secretion are still unclear. Here, we explored the etiology and underlying molecular mechanisms of glucagon dysregulation. Regular mice were fed by nutritionally modified diets for 16 weeks, and metabolic parameters were examined. The mice fed by highly protein-containing diet promptly exhibited glucose intolerance while smaller increase in body weight than regular diet-fed mice, together with significant elevation of plasma glucagon / insulin ratio suggesting its pathological impact. In vitro glucose load on glucagon-secreting cell-line InR1G induced hypersecretion of glucagon, and increase in oxidative stress and deterioration of insulin signaling were identified as underlying mechanisms. These data elucidate, at least partly, the previously unclear mechanism of abnormal glucagon secretion, providing insights into a potential novel approach to diabetes treatment, targeting glucagon.

Free Research Field

糖尿病