Differential mechanisms of glucose and palmitate in augmentation of insulin secretion in mouse pancreatic islets.
OBJECTIVE
To assess the possible importance of saturated fatty acids in glucose amplification of K+ATP channel-independent insulin secretion.


METHODS
Insulin release from perifused pancreatic islets of NMRI mice was determined by radioimmunoassay.


RESULTS
In the presence of K+ (20 mmol/l) and diazoxide (250 micromol/l), which stimulates Ca2+ influx and opens K+ATP channels, palmitate (165 micromol/l total; 1.2 micromol/l free) increased insulin secretion at 3.3, 10 and 16.7 mmol/l glucose while glucose (10; 16.7 mmol/l) did not increase insulin secretion. In the presence of K+ (60 mmol/l) and diazoxide (250 micromol/l), glucose (10; 16.7 mmol/l) stimulation of K+ATP channel-independent insulin secretion increased, whereas the effectiveness of palmitate (165 micromol/l total; 1.2 micromol/l free) on insulin secretion at both 3.3, 10 or 16.7 mmol/l glucose was reduced. Palmitate thereby mimicked the stimulatory pattern of the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (0.16 micromol/l), which also failed to increase insulin secretion at maximum depolarising concentrations of K+ (60 mmol/l). Furthermore, the protein kinase C inhibitor calphostin C (1 micromol/1), led to a complete suppression of the effects of both palmitate (165 micromol/l total; 1.2 micromol/l free) and myristate (165 micromol/l total; 2.4 micromol/l free) stimulation of glucose (16.7 mmol/l)-induced insulin secretion. Calphostin C (1 micromol/l), however, failed to affect insulin secretion induced by glucose (16.7 mmol/l).


CONCLUSIONS
These data suggest that glucose could increase insulin secretion independently of saturated fatty acids like palmitate and myristate, which amplify glucose-induced insulin secretion by activation of protein kinase C.
Thams
P
P
Department of Medical Biochemistry and Genetics, University of Copenhagen, Denmark.
Capito
K
K
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D046508:Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D019814:Myristic Acid / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010168:Palmitates / Q000494:pharmacology*; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007328:Insulin; D009281:Naphthalenes; D010168:Palmitates; D015221:Potassium Channels; D019814:Myristic Acid; D010171:Palmitoyl Coenzyme A; D005576:Colforsin; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; C058819:calphostin C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium