Acute hormonal effects on carnitine metabolism in thin and obese subjects: responses to somatostatin, glucagon, and insulin.
Plasma free carnitine and acylcarnitines were determined in man during acutely induced insulin deficiency. A 5-hr infusion of somatostatin at 6 microgram/min in 10 thin subjects produced profound, sustained hypoinsulinemia and led to rapid increases in plasma free fatty acids and ketoacids (peak increments of 0.67 mM each). Simultaneously, plasma free carnitine decreased, while plasma long-chain and short-chain acylcarnitines increased significantly. When hyperglucagonemia was created by inclusion of glucagon with the somatostatin, the hyperketonemia was reversed after 2 hr and the increase in acylcarnitine abolished. However, the decrease in free carnitine was accentuated. The antiketogenic effect of adding glucagon was due to an eventual breakthrough of the somatostatin blockade on insulin secretion, the latter gradually returning toward preinfusion levels. Inclusion of exogenous insulin with the somatostatin-glucagon infusion immediately lowered free fatty acids and ketoacids. Acylcarnitines also declined promptly, while the accelerated fall in free carnitine produced by glucagon was blunted by the addition of insulin. Qualitatively and quantitatively comparable results were seen in seven obese subjects. This study suggests: (1) the increase in plasma acylcarnitines previously described in fasting and diabetic ketosis is largely due to insulin deficiency; (2) the corresponding decrease in plasma free carnitine is attributable both to insulin deficiency and glucagon excess; and (3) the resistance of obese subjects to ketosis is unlikely to be due to deficits in carnitine or carnitine acyltransferases.
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002331:Carnitine / Q000097:blood*; D003920:Diabetes Mellitus / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon; D006801:Humans; D007328:Insulin / Q000097:blood; D007651:Keto Acids / Q000097:blood; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D013004:Somatostatin
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007651:Keto Acids; D013004:Somatostatin; D005934:Glucagon; D002331:Carnitine