Elucidation of the function of intestinal glucagon and the role of the intestine as a gluconeogenic organ

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16137
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Shiga University of Medical Science (2019); Asahikawa Medical College (2017-2018)
• Principal Investigator: Yanagimachi Tsuyoshi 滋賀医科大学, 医学部, 医員 (20596275)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: グルカゴン / 糖尿病

Outline of Final Research Achievements

Mice expressing the fluorescent protein Venus (YFP) under the promoter of the pro-glucagon gene were used to confirm glucagon expression. After the pancreas, stomach, and small intestine were removed, the glucagon of each organ was measured using a receptor-mediated method. Those organs glucagon levels of STZ mice were more elevated than that of control.
Since the method used in this study can not distinguish between glucagon and oxyntomodulin (OXM), NEP, which degrades glucagon, was added and evaluated. Glucagon activity in the pancreas and stomach was greatly reduced. On the other hand, in the small intestine, about 60% of the activity was retained in the diabetic state, suggesting that OXM may have been increased. We will analyze the effects of glucagon and OXM on glycogenesis in the intestinal tract.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

膵グルカゴンと異なり、膵外グルカゴンの分泌調節機構や生理学的な役割については検討されていない。既報では膵全的患者で経口ブドウ糖負荷後に免疫法で測定したグルカゴンの上昇を認めている。糖尿病状態での食後のグルカゴン分泌亢進に膵だけでなく、腸管グルカゴンが関与している可能性がある。この腸管グルカゴンの分泌機構を解明することが、糖尿病の病態を理解する上で重要と考えられる。さらに腸管での糖新生に関してはほとんど注目されておらず、報告も非常に少ない。腸管でのグルカゴン分泌や糖新生調節機構を明らかにすることは糖尿病の病態に新しい知見をもたらすことが期待され、新規治療法へのアプローチと成り得ると確信する。