Prevention of human diabetic ketoacidosis by somatostatin. Evidence for an essential role of glucagon.
To evaluate the role of glucagon in the pathogenesis of diabetic ketoacidosis in man, we studied the effect of suppression of glucagon secretion by somatostatin on changes in plasma beta-hydroxybutyrate and glucose concentrations (as well as changes in their precursors) after acute withdrawal of insulin from seven patients with juvenile-type diabetes. Suppression of glucagon secretion prevented the development of ketoacidosis for 18 hours after acute insulin withdrawal, whereas in control studies mild ketoacidosis occurred 10 hours after insulin was stopped. Plasma beta-hydroxybutyrate, glucose, free fatty acid, and glycerol levels were all markedly lower during suppression of glucagon secretion (p smaller than 0.001), whereas plasma alanine levels were higher (p smaller than 0.001). These studies indicate that insulin lack per se does not lead to fulminant diabetic ketoacidosis in man and that glucagon, by means of its gluconeogenic, ketogenic, and lipolytic actions, is a prerequisite to the development of this condition.
D000328:Adult; D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D003864:Depression, Chemical; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy; D016883:Diabetic Ketoacidosis / Q000209:etiology / Q000517:prevention & control*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D005990:Glycerol / Q000097:blood; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006885:Hydroxybutyrates / Q000097:blood; D006943:Hyperglycemia / Q000209:etiology; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D007657:Ketone Bodies / Q000097:blood; D007773:Lactates / Q000097:blood; D008297:Male; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D007657:Ketone Bodies; D007773:Lactates; D010455:Peptides; D013006:Growth Hormone; D005934:Glucagon; D000409:Alanine; D005990:Glycerol; D006854:Hydrocortisone