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Zhang, J.* ; Pivovarova-Ramich, O.* ; Kabisch, S.* ; Markova, M.* ; Hornemann, S.* ; Sucher, S.* ; Rohn, S.* ; Machann, J. ; Pfeiffer, A.F.H.*

High protein diets improve liver fat and insulin sensitivity by prandial but not fasting glucagon secretion in type 2 diabetes.

Front. Nutr. 9:808346 (2022)

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Glucagon (GCGN) plays a key role in glucose and amino acid (AA) metabolism by increasing hepatic glucose output. AA strongly stimulate GCGN secretion which regulates hepatic AA degradation by ureagenesis. Although increased fasting GCGN levels cause hyperglycemia GCGN has beneficial actions by stimulating hepatic lipolysis and improving insulin sensitivity through alanine induced activation of AMPK. Indeed, stimulating prandial GCGN secretion by isocaloric high protein diets (HPDs) strongly reduces intrahepatic lipids (IHLs) and improves glucose metabolism in type 2 diabetes mellitus (T2DM). Therefore, the role of GCGN and circulating AAs in metabolic improvements in 31 patients with T2DM consuming HPD was investigated. Six weeks HPD strongly coordinated GCGN and AA levels with IHL and insulin sensitivity as shown by significant correlations compared to baseline. Reduction of IHL during the intervention by 42% significantly improved insulin sensitivity [homeostatic model assessment for insulin resistance (HOMA-IR) or hyperinsulinemic euglycemic clamps] but not fasting GCGN or AA levels. By contrast, GCGN secretion in mixed meal tolerance tests (MMTTs) decreased depending on IHL reduction together with a selective reduction of GCGN-regulated alanine levels indicating greater GCGN sensitivity. HPD aligned glucose metabolism with GCGN actions. Meal stimulated, but not fasting GCGN, was related to reduced liver fat and improved insulin sensitivity. This supports the concept of GCGN-induced hepatic lipolysis and alanine- and ureagenesis-induced activation of AMPK by HPD.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Glucagon ; Insulin Sensitivity ; Liver Fat Content ; Alanine ; Type 2 Diabetes ; Non-alcoholic Fatty Liver Disease (nafld) ; High Protein Diet

ISSN (print) / ISBN 2296-861X

e-ISSN 2296-861X

Journal Frontiers in Nutrition

Quellenangaben Volume: 9, Article Number: 808346

Publisher Frontiers

Publishing Place Lausanne

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)

Grants Federal Ministry of Education & Research (BMBF)
German Federal Ministry of Food and Agriculture (BLE)
First Affiliated Hospital of Zhejiang Chinese Medical University