Impaired stimulation of gluconeogenesis during prolonged hypoglycemia in intensively treated insulin-dependent diabetic subjects.
Defective glucose counterregulation commonly seen in intensively treated insulin-dependent diabetes (IDDM) is mediated in part by a failure of compensatory stimulation of hepatic glucose production. Since the response of the liver to insulin-induced hypoglycemia normally involves activation of gluconeogenesis, we measured [14C]alanine conversion to [14C]glucose (a qualitative index of gluconeogenesis) and glucose production (using [3-3H]glucose) in seven intensively treated type I diabetic subjects (hemoglobin-A1, 7.1 +/- 0.4%) during low dose infusion of insulin (0.3 mU/kg.min for 210 min). IDDM patients received insulin overnight to maintain euglycemia before study. Although insulin levels rose to a similar extent as those in normal control subjects (n = 6), the fall in plasma glucose was markedly greater in IDDM (2.5 +/- 0.2 vs. 3.64 +/- 0.2 mM in controls; P < 0.01). The glucagon response was totally lost in IDDM, and epinephrine release was delayed and slightly reduced compared to that in control subjects. In contrast to that in normal subjects, hepatic glucose production in the IDDM subjects remained persistently suppressed by about 60% throughout the study. The conversion of alanine and lactate to glucose remained virtually unchanged in the IDDM, whereas in controls it increased 2-fold above baseline during the last hour of the study. Our data suggest that the failure of gluconeogenesis to increase during hypoglycemia is an important factor contributing to the defective hepatic response observed in the intensively treated type I diabetic subjects.
Caprio
S
S
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510.
Napoli
R
R
Saccà
L
L
Tamborlane
W V
WV
Sherwin
R S
RS
D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D004837:Epinephrine / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis / Q000502:physiology*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D007328:Insulin / Q000009:adverse effects* / Q000097:blood; D008297:Male; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D004837:Epinephrine