Glucagon under high fat diet induced obesity

Introduction: Hyperglucagonemia has been described in obesity and type 2 diabetes, but its development and pathogenic role have been only sparsly investigated. Therefore, we examined whether hyperglucagonemia is also present in a rodent model of the metabolic syndrome, the high fat fed rat. Using different fat types, we also analyzed in vivo and in vitro whether glucagon secretion is functionally connected to specific fatty acid milieus.

Methods: Male Wistar rats were fed either a standard diet (10 En% lard [SC]) or high fat diets (42% En% lard [HF-L] or olive oil [HF-O]) for 12 weeks. Serum glucagon as well as islet glucagon content and islet preproglucagon mRNA were measured. In parallel to this in vivo approach, glucagonotropic effects of different FFA mixtures with varying molar ratios of palmitate [LC-SFA] and oleate [MUFA] were assessed in freshly isolated islets of normal animals.

Results: In comparison to SC, serum glucagon was 2.3fold (p=0.04) higher in HF-L and 1.9fold (p=0.03) higher in HF-O, while the intrainsular glucagon and preproglucagon-mRNA content did not differ significantly among the SC- and the HF-groups. In vitro, LC-SFA predominant FFA mixtures led to a 1.4fold (p=0.03) and the MUFA-predominant FFA mixtures to a 1.7fold (p=0.01) increase in alpha-cellular glucagon release compared to untreated controls at 5.6 mM glucose. There was no statistical difference between LC-SFA and MUFA mixtures.

Conclusions: Hyperglucagonemia in obesity and type 2 diabetes might evolve from direct secretory effects of free fatty acids on the pancreatic alpha-cell. The expression of preproglucagon is not affected by hyperlipacidemia. So far, there is no evidence for potential dietary differences between LC-SFA (→ Lard → Western Diet) and MUFA (→ Olive Oil → Mediterranean Diet).