TY - JOUR

T1 - Studies of insulin resistance in congenital generalized lipodystrophy

AU - Søvik, O

AU - Vestergaard, H

AU - Trygstad, O

AU - Pedersen, O

PY - 1996/6

Y1 - 1996/6

N2 - Two well-characterized patients with congenital, generalized lipodystrophy have been studied by the euglycaemic hyperinsulinaemic clamp technique in combination with indirect calorimetry. Furthermore, glycogen synthase in muscle biopsies was studied in one patient with regard to enzyme activity, immunoreactive protein and mRNA levels. The patients had fasting hyperinsulinaemia, and the rate of total glucose disposal was severely impaired, primarily due to a decreased non-oxidative glucose metabolism. In the patient studied with muscle biopsy, the expected activation of glycogen synthase by insulin did not occur. In both patients there was severely increased hepatic glucose output in the basal state, suggesting a failure of insulin to suppress hepatic gluconeogenesis. During insulin infusion a substantially elevated rate of lipid oxidation remained in the patients, in contrast to the almost completely suppressed lipid oxidation in the controls. It is concluded that patients with congenital generalized lipodystrophy may present severe insulin resistance with regard to hepatic glucose production as well as muscle glycogen synthesis and lipid oxidation. The results suggest a postreceptor defect in the action of insulin in congenital generalized lipodystrophy. The further localization of such a defect is hampered by the still incomplete understanding of the pathways that link insulin-stimulated tyrosine phosphorylation to the ultimate action of insulin upon target cells.

AB - Two well-characterized patients with congenital, generalized lipodystrophy have been studied by the euglycaemic hyperinsulinaemic clamp technique in combination with indirect calorimetry. Furthermore, glycogen synthase in muscle biopsies was studied in one patient with regard to enzyme activity, immunoreactive protein and mRNA levels. The patients had fasting hyperinsulinaemia, and the rate of total glucose disposal was severely impaired, primarily due to a decreased non-oxidative glucose metabolism. In the patient studied with muscle biopsy, the expected activation of glycogen synthase by insulin did not occur. In both patients there was severely increased hepatic glucose output in the basal state, suggesting a failure of insulin to suppress hepatic gluconeogenesis. During insulin infusion a substantially elevated rate of lipid oxidation remained in the patients, in contrast to the almost completely suppressed lipid oxidation in the controls. It is concluded that patients with congenital generalized lipodystrophy may present severe insulin resistance with regard to hepatic glucose production as well as muscle glycogen synthesis and lipid oxidation. The results suggest a postreceptor defect in the action of insulin in congenital generalized lipodystrophy. The further localization of such a defect is hampered by the still incomplete understanding of the pathways that link insulin-stimulated tyrosine phosphorylation to the ultimate action of insulin upon target cells.

KW - Calorimetry, Indirect

KW - Female

KW - Glucose

KW - Glucose Clamp Technique

KW - Glycogen Synthase

KW - Humans

KW - Hyperinsulinism

KW - Insulin Resistance

KW - Lipid Metabolism

KW - Lipodystrophy

KW - Male

KW - Middle Aged

M3 - Journal article

C2 - 8783770

VL - 413

SP - 29

EP - 37

JO - Acta Paediatrica, International Journal of Paediatrics, Supplement

JF - Acta Paediatrica, International Journal of Paediatrics, Supplement

SN - 0803-5326

ER -