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Schuppelius, B.* ; Schüler, R.* ; Pivovarova-Ramich, O.* ; Hornemann, S.* ; Busjahn, A.* ; Machann, J. ; Kruse, M.* ; Park, S.Q.* ; Kabisch, S.* ; Csanalosi, M.* ; Ost, A.C.* ; Pfeiffer, A.F.H.*

Alterations in glucagon levels and the glucagon-to-insulin ratio in response to high dietary fat or protein intake in healthy lean adult twins: A post hoc analysis.

Nutrients 16:3905 (2024)

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Background/Objectives: Emerging data support evidence of the essential role of glucagon for lipid metabolism. However, data on the role of dietary fat intake for glucagon secretion is limited. This analysis investigated whether altering nutritional fat intake affects glucagon levels in healthy subjects. Methods: A total of 92 twins (age: 31 ± 14 years, BMI: 23 ± 3 kg/m²) consumed two 6-week diets: first a low-fat, high-carbohydrate diet (LFD) followed by an isocaloric high-fat, low-carbohydrate diet (HFD). In total, 24 twins (age: 39 ± 15 years, BMI: 24 ± 2 kg/m²) continued with a high-protein diet (HPD). Clinical investigations were performed after 6 weeks of the LFD, after 1 and 6 weeks of the HFD and after 6 weeks of the HPD. Results: The LFD caused a significant decrease in fasting glucagon (-27%, p < 0.001) compared to baseline. After 6 weeks of the HFD, glucagon increased (117%, p < 0.001 vs. LFD), while free fatty acids decreased. Six weeks of the HPD further increased glucagon levels (72%, p = 0.502 vs. HFD), although fasting amino acid levels remained constant. Fasting insulin and HOMA-IR moderately increased after one week of the HFD, while six weeks of the HPD significantly decreased both. The fasting glucagon-to-insulin ratio decreased during the LFD (p < 0.001) but increased after the HFD (p < 0.001) and even further increased after the HPD (p = 0.018). Liver fat, triglycerides and blood glucose did not increase during the HFD. The heritability of glucagon levels was 45% with the LFD. Conclusions: An HFD increases glucagon levels and the glucagon-to-insulin ratio under isocaloric conditions compared to an LFD in healthy lean subjects. This rise in glucagon may represent a metabolic response to prevent hepatic steatosis, as glucagon increases have been previously shown to induce hepatic fat oxidation.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Glucagon ; Healthy Twins ; Heritability ; High-fat Diet ; High-protein Diet ; Insulin ; Low-fat Diet; Pulsatile Insulin; Inverse Relationship; Amino-acids; Alpha-cells; Secretion; Glucose; Metabolism; Incretin; Alanine; Suppression

ISSN (print) / ISBN 2072-6643

e-ISSN 2072-6643

Journal Nutrients

Quellenangaben Volume: 16, Issue: 22, Article Number: 3905

Publisher MDPI

Publishing Place Basel

Non-patent literature Publications

Reviewing status Peer reviewed

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

Grants German Federal Ministry of Education and Research (BMBF)
Federal Ministry of Education and Research