Stimulatory short-term effects of free fatty acids on glucagon secretion at low to normal glucose concentrations☆
Section snippets
Materials
Radioimmunoassays for pancreatic glucagon (crossreactivity to oxyntomodulin <0.1%) and for immunoreactive insulin (IRI) were performed with kits from Linco Research (St Louis, MO). Fatty acid ultra-free bovine serum albumin (BSA, Fraction V), protease inhibitor cocktail (Complete), Collagenase P (1.5 U · mg−1), as well as all technical and chemical equipment for semiquantitative Light Cycler Polymerase Chain Reaction (PCR), were from Roche Diagnostics (Mannheim, Germany). Reverse transcription
Time- and glucose-dependent effects of palmitate on glucagon and insulin secretion
At 2.8 mmol/L glucose, palmitate elicited a 1.7- to 2.7-fold (ie, in average a 2.0 [±0.3]-fold) increase in glucagon secretion over 30 minutes (P = .041), 60 minutes (P = .0003), 120 minutes (P = .001), and 240 minutes (P = .0003). The glucagonotropic effect was fading after 480 minutes (Fig 1A). At concomitant 16.7 mmol/L glucose, no relevant glucagonotropic palmitate effect was observed (Fig 1B). Comparing glucagon secretion at 16.7 mmol/L glucose with that at 2.8 mmol/L glucose, we could
Discussion
In the present study, palmitate and oleate induced a relevant increase of glucagon secretion from isolated rat pancreatic islets during short-term exposure (ie, ≤4 hours). This glucagonotropic effect was only observed at low to normal glucose levels (2.8 to 5.6 mmol/L) but not at high glucose (16.7 mmol/L). A decrease of the glucose concentration per se (ie, in the absence of FFA) exerted no relevant glucagonotropic effect, which is in accordance to previous in vitro studies.6, 11, 19 Ishishara
Acknowledgements
The authors acknowledge the excellent technical assistance of Iris Ottinger. They are also indebted to Dr Christa Buechler for helpful discussions.
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Supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (Bo 1379/2-1, Bo 1379/2-2).