Stimulatory short-term effects of free fatty acids on glucagon secretion at low to normal glucose concentrations.
While free fatty acids (FFA) are well known as insulin secretagogues, their effects on pancreatic alpha cells have been mostly neglected. In the present study we therefore systematically analyzed the glucagon metabolism of rat pancreatic islets under the influence of FFA. Primary islets were incubated in the presence or absence of 200 micromol/L albumin-complexed palmitate or oleate at 2.8 mmol/L versus 16.7 mmol/L glucose and glucagon secretion was monitored over 8 hours. In addition to these time-course experiments, dose dependency of palmitate-induced effects was tested by a 2-hour incubation with 50 to 300 micromol/L albumin-complexed palmitate at 2.8 mmol/L and 5.6 mmol/L glucose. Apart from glucagon secretion, intracellular immunoreactive glucagon and cellular preproglucagon-mRNA (PPG-mRNA) content were determined from the remaining cell lysates. FFA, especially palmitate, induced a significant and dose-dependent increase of glucagon secretion (in average 2-fold above control) during the first 120 minutes of incubation at low to normal glucose (2.8 and 5.6 mmol/L). There was no significant glucagonotropic effect of FFA at concomitant 16.7 mmol/L glucose. Intracellular glucagon as well as cellular PPG-mRNA content were found to be dose-dependently diminished by palmitate when compared with untreated controls at 5.6 mmol/L glucose. The present analysis therefore points to a new role for FFA as a nutritient secretagogue and a modulator of alpha-cellular glucagon metabolism.
Bollheimer
L Cornelius
LC
Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany.
Landauer
Heike C
HC
Troll
Stephanie
S
Schweimer
Joachim
J
Wrede
Christian E
CE
Schölmerich
Jürgen
J
Buettner
Roland
R
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000378:metabolism* / Q000494:pharmacology; D005934:Glucagon / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019301:Oleic Acid / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D052336:Proglucagon; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000418:Albumins; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D011498:Protein Precursors; D012333:RNA, Messenger; D019301:Oleic Acid; D019308:Palmitic Acid; D052336:Proglucagon; D005934:Glucagon