Adiponectin and its response to thiazolidinediones are associated with insulin-mediated glucose metabolism in type 2 diabetic patients and their first-degree relatives

V Hulstrøm, K Højlund, J Vinten, H Beck-Nielsen, K Levin

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2008-Feb-18
OriginalsprogEngelsk
TidsskriftDiabetes, Obesity and Metabolism
ISSN1462-8902
DOI
StatusUdgivet - 18. feb. 2008

Fingeraftryk

Thiazolidinediones
Adiponectin
Insulin
troglitazone
Type 2 Diabetes Mellitus
Insulin Resistance
Adipose Tissue
Glycogen Synthase
Glucose Clamp Technique
Lipid Metabolism
Up-Regulation
Lipids
Weights and Measures

Citer dette

@article{afd48e40422c11dd9fbe000ea68e967b,
title = "Adiponectin and its response to thiazolidinediones are associated with insulin-mediated glucose metabolism in type 2 diabetic patients and their first-degree relatives",
abstract = "Patients with type 2 diabetes (T2D) and their first-degree relatives (FDRs) are characterized by hypoadiponectinaema and insulin resistance. In T2D patients, plasma adiponectin and insulin sensitivity (SI) increase in response to thiazolidinediones (TZDs). These findings suggest a role for adiponectin in the regulation of SI. We studied the relationship between plasma adiponectin and glucose and lipid metabolism and the effect of troglitazone (200 mg/day) for 12 weeks in 19 normoglycaemic, obese FDR and 20 obese T2D patients, using euglycaemic-hyperinsulinaemic clamps, glycolytic flux calculations and indirect calorimetry. Plasma adiponectin was similar in both groups, despite higher glucose disposal (Rd), glucose oxidation and glycolytic flux and lower lipid oxidation during insulin stimulation in FDR compared with T2D patients. Plasma adiponectin correlated with insulin-stimulated Rd, non-oxidative glucose disposal (NOGD), glucose storage and SI in both groups after adjustment for sex and body fat. The troglitazone-mediated upregulation of plasma adiponectin was associated with increased insulin-stimulated Rd, NOGD and glucose storage in both groups. No effect on endogenous glucose production was observed. In FDR, plasma adiponectin correlated with insulin-stimulated glycogen synthase activity and the troglitazone-induced increase in plasma adiponectin correlated with the improvement in insulin-stimulated Rd and SI after adjustment for sex and body fat. In conclusion, plasma adiponectin in weight-matched FDR and T2D patients is comparably low and correlates with insulin-mediated glucose uptake and storage. Moreover, these data provide evidence for an adiponectin-dependent insulin-sensitizing effect of TZDs at an early stage before development of T2D and that this effect is exerted mainly on insulin-mediated glucose metabolism.",
author = "V Hulstr{\o}m and K H{\o}jlund and J Vinten and H Beck-Nielsen and K Levin",
year = "2008",
month = "2",
day = "18",
doi = "10.1111/j.1463-1326.2008.00854.x",
language = "English",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
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TY - JOUR

T1 - Adiponectin and its response to thiazolidinediones are associated with insulin-mediated glucose metabolism in type 2 diabetic patients and their first-degree relatives

AU - Hulstrøm, V

AU - Højlund, K

AU - Vinten, J

AU - Beck-Nielsen, H

AU - Levin, K

PY - 2008/2/18

Y1 - 2008/2/18

N2 - Patients with type 2 diabetes (T2D) and their first-degree relatives (FDRs) are characterized by hypoadiponectinaema and insulin resistance. In T2D patients, plasma adiponectin and insulin sensitivity (SI) increase in response to thiazolidinediones (TZDs). These findings suggest a role for adiponectin in the regulation of SI. We studied the relationship between plasma adiponectin and glucose and lipid metabolism and the effect of troglitazone (200 mg/day) for 12 weeks in 19 normoglycaemic, obese FDR and 20 obese T2D patients, using euglycaemic-hyperinsulinaemic clamps, glycolytic flux calculations and indirect calorimetry. Plasma adiponectin was similar in both groups, despite higher glucose disposal (Rd), glucose oxidation and glycolytic flux and lower lipid oxidation during insulin stimulation in FDR compared with T2D patients. Plasma adiponectin correlated with insulin-stimulated Rd, non-oxidative glucose disposal (NOGD), glucose storage and SI in both groups after adjustment for sex and body fat. The troglitazone-mediated upregulation of plasma adiponectin was associated with increased insulin-stimulated Rd, NOGD and glucose storage in both groups. No effect on endogenous glucose production was observed. In FDR, plasma adiponectin correlated with insulin-stimulated glycogen synthase activity and the troglitazone-induced increase in plasma adiponectin correlated with the improvement in insulin-stimulated Rd and SI after adjustment for sex and body fat. In conclusion, plasma adiponectin in weight-matched FDR and T2D patients is comparably low and correlates with insulin-mediated glucose uptake and storage. Moreover, these data provide evidence for an adiponectin-dependent insulin-sensitizing effect of TZDs at an early stage before development of T2D and that this effect is exerted mainly on insulin-mediated glucose metabolism.

AB - Patients with type 2 diabetes (T2D) and their first-degree relatives (FDRs) are characterized by hypoadiponectinaema and insulin resistance. In T2D patients, plasma adiponectin and insulin sensitivity (SI) increase in response to thiazolidinediones (TZDs). These findings suggest a role for adiponectin in the regulation of SI. We studied the relationship between plasma adiponectin and glucose and lipid metabolism and the effect of troglitazone (200 mg/day) for 12 weeks in 19 normoglycaemic, obese FDR and 20 obese T2D patients, using euglycaemic-hyperinsulinaemic clamps, glycolytic flux calculations and indirect calorimetry. Plasma adiponectin was similar in both groups, despite higher glucose disposal (Rd), glucose oxidation and glycolytic flux and lower lipid oxidation during insulin stimulation in FDR compared with T2D patients. Plasma adiponectin correlated with insulin-stimulated Rd, non-oxidative glucose disposal (NOGD), glucose storage and SI in both groups after adjustment for sex and body fat. The troglitazone-mediated upregulation of plasma adiponectin was associated with increased insulin-stimulated Rd, NOGD and glucose storage in both groups. No effect on endogenous glucose production was observed. In FDR, plasma adiponectin correlated with insulin-stimulated glycogen synthase activity and the troglitazone-induced increase in plasma adiponectin correlated with the improvement in insulin-stimulated Rd and SI after adjustment for sex and body fat. In conclusion, plasma adiponectin in weight-matched FDR and T2D patients is comparably low and correlates with insulin-mediated glucose uptake and storage. Moreover, these data provide evidence for an adiponectin-dependent insulin-sensitizing effect of TZDs at an early stage before development of T2D and that this effect is exerted mainly on insulin-mediated glucose metabolism.

U2 - 10.1111/j.1463-1326.2008.00854.x

DO - 10.1111/j.1463-1326.2008.00854.x

M3 - Journal article

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

ER -