The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine.
Available information on the fate and insulinotropic action of L-alanine in isolated pancreatic islets is restricted to data collected in obese hyperglycemic mice. Recent data, however, collected mostly in tumoral islet cells of either the RINm5F line or BRIN-BD11 line, have drawn attention to the possible role of Na(+) co-transport in the insulinotropic action of L-alanine. In the present study conducted in islets prepared from normal adult rats, L-alanine was found (i) to inhibit pyruvate kinase in islet homogenates, (ii) not to affect the oxidation of endogenous fatty acids in islets prelabelled with [U-14C]palmitate, (iii) to stimulate 45Ca uptake in islets deprived of any other exogenous nutrient, and (iv) to augment insulin release evoked by either 2-ketoisocaproate or L-leucine, whilst failing to significantly affect glucose-induced insulin secretion. The oxidation of L-[U-14C]alanine was unaffected by D-glucose, but inhibited by L-leucine. Inversely, L-alanine decreased the oxidation of D-[U-14C]glucose, but failed to affect L-[U-14C]leucine oxidation. It is concluded that the occurrence of a positive insulinotropic action of L-alanine is restricted to selected experimental conditions, the secretory data being compatible with the view that stimulation of insulin secretion by the tested nutrient(s) reflects, as a rule, their capacity to augment ATP generation in the islet B cells. However, the possible role of Na(+) co-transport in the secretory response to L-alanine cannot be ignored.
Sener
Abdullah
A
Faculty of Medicine, Laboratory of Experimental Medicine, Brussels Free University, 808 Route de Lennik, Belgium.
Malaisse
Willy J
WJ
D000409:Alanine / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D002250:Carbon Radioisotopes; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D007930:Leucine / Q000494:pharmacology; D010084:Oxidation-Reduction; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors; D051381:Rats; D013997:Time Factors
D002132:Calcium Radioisotopes; D002250:Carbon Radioisotopes; D007328:Insulin; D011770:Pyruvate Kinase; D007930:Leucine; D005947:Glucose; D000409:Alanine; D002118:Calcium