Meal-derived glucagon responses are related to lower hepatic phosphate concentrations in obesity and type 2 diabetes

K. S. Weber, K. Strassburger, M. Fritsch, A. Bierwagen, C. Koliaki, E. Phielix, G. Pacini, J-H Hwang, D. F. Markgraf, Roman Burkart, K. Muessig, J. Szendroedi, M. Roden*

*Corresponding author for this work

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Abstract

Aim. - Type 2 diabetes (T2D) alters glucagon, glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide (GIP) and hepatic energy metabolism, yet the possible relationships remain unclear.

Methods. - In this observational study, lean insulin-sensitive control subjects (BMI: 23.2 +/- 1.5 kg/m(2)), age-matched insulin-resistant obese subjects (BMI: 34.3 +/- 1.7 kg/m(2)) and similarly obese elderly T2D patients (BMI: 32.0 +/- 2.4 kg/m(2)) underwent mixed-meal tolerance tests (MMTTs), and assessment of hepatic gamma ATP, inorganic phosphate (P-i) and lipids using P-31/H-1 magnetic resonance spectroscopy. Meal-induced secretion of glucagon and incretins was calculated from incremental areas under the concentration-time curves (iAUCs). Peripheral and adipose tissue insulin sensitivity were assessed from time courses of circulating glucose, insulin and free fatty acids.

Results. - MMTT-derived peripheral insulin sensitivity was lowest in T2D patients (P <0.001), while glucagon concentrations were comparable across all three groups. At 260 min, GLP-1 was lower in T2D patients than in controls, whereas GIP was lowest in obese individuals. Fasting glucagon concentrations correlated positively with fasting (r = 0.60) and postprandial hepatocellular lipid levels (160 min: r= 0.51, 240 min: r = 0.59), and negatively with adipose tissue insulin sensitivity (r = -0.73). Higher meal-induced glucagon release (iAUC(0)(-260) (min)) correlated with lower fasting (r = -0.62) and postprandial P(i )levels (160 min: r = -0.43, 240 min: r = -0.42; all P <0.05). Higher meal-induced release of GIP (iAUC(0-260) (min)) correlated positively with fasting (r = 0.54) and postprandial serum triglyceride concentrations (iAUC(0-260 min, )r = 0.54; all P <0.01).

Conclusion. - Correlations between fasting glucagon and hepatic lipids and between meal-induced glucagon and hepatic P-i suggest a role for glucagon in hepatic energy metabolism. (C) 2018 Elsevier Masson SAS. All rights reserved.

Original languageEnglish
Pages (from-to)444-448
Number of pages5
JournalDiabetes & Metabolism
Volume44
Issue number5
DOIs
Publication statusPublished - Nov 2018

Keywords

  • Adipose tissue
  • Glucagon
  • GIP
  • GLP-1
  • Hepatic fat content
  • Insulin sensitivity
  • CELL FUNCTION
  • GLUCONEOGENESIS
  • INSULIN

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