Effects of acute insulin excess and deficiency on gluconeogenesis and glycogenolysis in type 1 diabetes.
To determine whether insulin induces acute changes in endogenous glucose production (EGP) via changes in gluconeogenesis (GNG), glycogenolysis (GL), or both, we measured GNG (with (2)H(2)O) and GL (EGP-GNG) in nine patients with type 1 diabetes during acute insulin excess produced by subcutaneous injection of insulin and during insulin deficiency which developed between 5 and 8 h after insulin injection. During insulin excess, free insulin concentration rose fivefold (from 36 to 180 pmol/l). Plasma glucose was maintained between 6.2 and 6.7 mmol/l for approximately 4 h with IV glucose. EGP (with 6,6-(2)H glucose) decreased from 17.1 to 9.8 micro mol. kg(-1). min(-1) after 1 h. This decrease was almost completely accounted for by a decrease in GL (from 10.7 to 4.6 micro mol. kg(-1). min(-1)). During insulin deficiency, plasma glucose rose from 6.2 to 10.5 mmol/l and EGP from 9.5 to 14.3 micro mol/kg min. The increase in EGP again was accounted for by an increase in GL. We conclude that in type 1 diabetes acute regulation of EGP by insulin is mainly via changes in GL while GNG changes little during the early hours of acute insulin excess or deficiency.
Boden
Guenther
G
Division of Endocrinology/Diabetes/Metabolism and the General Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Cheung
Peter
P
Homko
Carol
C
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D050260:Carbohydrate Metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005943:Gluconeogenesis / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage / Q000096:biosynthesis / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism*; D006728:Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000172:deficiency* / Q000378:metabolism*; D007657:Ketone Bodies / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D010084:Oxidation-Reduction
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007328:Insulin; D007657:Ketone Bodies; D008055:Lipids; D006003:Glycogen; D005947:Glucose