Increased Lactate Release per Fat Cell in Normoglycemic First-Degree Relatives of Individuals With Type 2 Diabetes

Sandqvist, Madeléne; Eriksson, Jan W.; Jansson, Per-Anders E.

doi:10.2337/diabetes.50.10.2344

Cited by 25 publications

(15 citation statements)

References 64 publications

(71 reference statements)

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“…In vivo lactate release from subcutaneous abdominal adipose tissue has previously been found to be higher in FDR rthan in CON (47), and these findings suggest that an increased uptake and turnover of glucose in adipose tissue is a primary defect in the development of type 2 diabetes. Furthermore, Eriksson et al (14) found less efficient inhibition of in vivo lipolysis by insulin in subcutaneous abdominal adipose tissue of FDR compared with CON, and it thus seems that subcutaneous abdominal adipose tissue metabolite turnover (glucose, lactate, lipids) in general is increased in FDR.…”

Section: Adipose Tissue and Skeletal Muscle Metabolismmentioning

confidence: 78%

Effect of physical training on insulin secretion and action in skeletal muscle and adipose tissue of first-degree relatives of type 2 diabetic patients

Dela

Stallknecht

2010

American Journal of Physiology-Endocrinology and Metabolism

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Dela F, Stallknecht B. Effect of physical training on insulin secretion and action in skeletal muscle and adipose tissue of firstdegree relatives of type 2 diabetic patients. Am J Physiol Endocrinol Metab 299: E80 -E91, 2010. First published April 20, 2010; doi:10.1152/ajpendo.00765.2009.-Physical training affects insulin secretion and action, but there is a paucity of data on the direct effects in skeletal muscle and adipose tissue and on the effect of training in first-degree relatives (FDR) of patients with type 2 diabetes. We studied insulin action at the whole body level and peripherally in skeletal muscle and adipose tissue as well as insulin-secretory capacity in seven FDR and eight control (CON) subjects before and after 12 wk of endurance training. Training improved physical fitness. Insulinmediated glucose uptake (GU) increased (whole body and leg; P Ͻ 0.05) after training in CON but not in FDR, whereas glucose-mediated GU increased (P Ͻ 0.05) in both groups. Adipose tissue GU was not affected by training, but it was higher (abdominal, P Ͻ 0.05; femoral, P ϭ 0.09) in FDR compared with CON. Training increased skeletal muscle lipolysis (P Ͻ 0.05), and it was markedly higher (P Ͻ 0.05) in subcutaneous abdominal than in femoral adipose tissue and quadriceps muscle with no difference between FDR and CON. Glucosestimulated insulin secretion was lower in FDR compared with CON, but no effect of training was seen. Glucagon-like peptide-1 stimulated insulin secretion five-to sevenfold. We conclude that insulin-secretory capacity is lower in FDR than in CON and that there is dissociation between training-induced changes in insulin secretion and insulin-mediated GU. Maximal GU rates are similar between groups and increases with physical training.glucagon-like peptide-1; hyperglycemic clamp; blood flow; intravenous glucose tolerance test; hyperinsulinemic euglycemic clamp; microdialysis; arteriovenous balance PHYSICAL TRAINING IS A CORNERSTONE in the initial treatment of patients with type 2 diabetes. In skeletal muscle, the insulinsensitizing effect of training in both healthy individuals and patients with type 2 diabetes is well documented (6,8,10,34,46). In individuals with a genetic predisposition for type 2 diabetes, first-degree relatives (FDR) of patients with type 2 diabetes, only a few training studies have been carried out, and none have directly examined the effect of physical training on insulin sensitivity in skeletal muscle and adipose tissue. In one study in a mixed group of FDR males and females, training enhanced insulin-mediated whole body glucose uptake rates (40), but there was no correlation between glucose uptake and measures of fitness [maximal oxygen uptake (V O 2max )]. In a recent study in females (3), a training-induced increase in whole body insulin sensitivity was found only in FDR subjects, yet this could not be demonstrated in control subjects (CON) despite similar increases in V O 2max in the two groups.

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Section: Adipose Tissue and Skeletal Muscle Metabolismmentioning

confidence: 78%

Effect of physical training on insulin secretion and action in skeletal muscle and adipose tissue of first-degree relatives of type 2 diabetic patients

Dela

Stallknecht

2010

American Journal of Physiology-Endocrinology and Metabolism

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“…All buffers and media were adjusted to pH 7.4. After 24 h of resting, cells were incubated with or without glucose at different concentrations (5.0, 8.3 and 11.1 mmol/l) for up to 4 h. Further co-incubations with standard concentrations of insulin (600 pmol/l) [13] and the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor wortmannin (100 nmol/l) [14], protein kinase B (AKT) inhibitor (10 μmol/l) [15] (both Alexis, Lausen, Switzerland) and insulin-receptor antibody (20 nmol/l, Ab 3; Labvision, Fremont, CA, USA) [16] were tested. Supernatants of the culture media were stored and analysed for visfatin concentrations.…”

Section: Cell Culture Experimentsmentioning

confidence: 99%

The release of the adipocytokine visfatin is regulated by glucose and insulin

et al. 2006

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Aims/hypothesis The novel insulin-mimetic adipocytokine visfatin has been linked to the metabolic syndrome, but its regulation has not been characterised to date. Since insulinmimetic actions of visfatin may be part of the feedback regulation of glucose homeostasis, we hypothesised that visfatin concentrations are influenced by glucose or insulin blood levels in humans. Subjects, materials and methods In this randomised, doubleblind, placebo-controlled crossover study, nine healthy male subjects (age 26±6 years) attended three different study days. On each day, systemic glucose concentrations of 5.0, 8.3 and 11.1 mmol/l were attained by stepwise increases in i.v. infusions of glucose, representing fasting and postprandial conditions. Visfatin plasma concentrations were studied during concomitant exogenous hyperinsulinaemia, inhibition of endogenous insulin production by somatostatin infusion, and placebo time control. Additionally, human adipocytes were cultured to study visfatin release and mRNA expression in vitro.Results Glucose concentrations of 8.3 and 11.1 mmol/l increased circulating visfatin from baseline concentrations of 0.5±0.0 ng/ml to 0.9±0.1 and 2.1±0.3 ng/ml, respectively (p<0.01). Glucose-induced elevation of visfatin was prevented by co-infusion of insulin or somatostatin (p<0.05). Cultured subcutaneous and visceral adipocytes released an equivalent amount of visfatin upon glucose-concentrationand time-dependent stimulation. Visfatin secretion involved the phosphatidylinositol 3-kinase (PI3-kinase) and protein kinase B (AKT) pathways. The mRNA expression pattern of visfatin was consistent with this altered protein release. Conclusions/interpretation Circulating visfatin concentrations are increased by hyperglycaemia. This effect is suppressed by exogenous hyperinsulinaemia or somatostatin infusion. Glucose signalling for visfatin release in adipocytes involves the PI3-kinase/AKT pathway.

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“…Although AT is of minor quantitative importance for whole-body glucose disposal, the tissue produces lactate (11), which functions as a gluconeogenic precursor in the liver (12). Previous studies have demonstrated increased plasma lactate (13) and lactate release from adipocytes (14) in FDR subjects.…”

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confidence: 99%

Impact of Physical Inactivity on Subcutaneous Adipose Tissue Metabolism in Healthy Young Male Offspring of Patients With Type 2 Diabetes

et al. 2010

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OBJECTIVEPhysical inactivity is a risk factor for type 2 diabetes and may be more detrimental in first-degree relative (FDR) subjects, unmasking underlying defects of metabolism. Using a positive family history of type 2 diabetes as a marker of increased genetic risk, the aim of this study was to investigate the impact of physical inactivity on adipose tissue (AT) metabolism in FDR subjects.RESEARCH DESIGN AND METHODSA total of 13 FDR and 20 control (CON) subjects participated in the study. All were studied before and after 10 days of bed rest using the glucose clamp technique combined with measurements of glucose uptake, lipolysis, and lactate release from subcutaneous abdominal (SCAAT) and femoral (SCFAT) adipose tissue by the microdialysis technique. Additionally, mRNA expression of lipases was determined in biopsies from SCAAT.RESULTSBefore bed rest, the FDR subjects revealed significantly increased glucose uptake in SCAAT. Furthermore, mRNA expression of lipases was significantly decreased in the SCAAT of FDR subjects. Bed rest significantly decreased lipolysis and tended to increase glucose uptake in the SCFAT of both CON and FDR subjects. In response to bed rest, SCAAT glucose uptake significantly increased in CON subjects but not in FDR subjects.CONCLUSIONSFDR subjects exhibit an abnormal AT metabolism including increased glucose uptake prior to bed rest. However, the differences between FDR and CON subjects in AT metabolism were attenuated during bed rest due to relatively more adverse changes in CON subjects compared with FDR subjects. Physical inactivity per se is not more deleterious in FDR subjects as compared with CON subjects with respect to derangements in AT metabolism.

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Increased Lactate Release per Fat Cell in Normoglycemic First-Degree Relatives of Individuals With Type 2 Diabetes

Cited by 25 publications

References 64 publications

Effect of physical training on insulin secretion and action in skeletal muscle and adipose tissue of first-degree relatives of type 2 diabetic patients

Effect of physical training on insulin secretion and action in skeletal muscle and adipose tissue of first-degree relatives of type 2 diabetic patients

The release of the adipocytokine visfatin is regulated by glucose and insulin

Impact of Physical Inactivity on Subcutaneous Adipose Tissue Metabolism in Healthy Young Male Offspring of Patients With Type 2 Diabetes

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