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

OBJECTIVE Physical 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 METHODS A 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. RESULTS Before 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. CONCLUSIONS FDR 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.

[1]  A. Consoli,et al.  Mechanism of increased gluconeogenesis in noninsulin-dependent diabetes mellitus. Role of alterations in systemic, hepatic, and muscle lactate and alanine metabolism. , 1990, The Journal of clinical investigation.

[2]  J. Bülow,et al.  Effect of training on epinephrine-stimulated lipolysis determined by microdialysis in human adipose tissue. , 1995, The American journal of physiology.

[3]  P. Jansson,et al.  Increased lactate release per fat cell in normoglycemic first-degree relatives of individuals with type 2 diabetes. , 2001, Diabetes.

[4]  F. Dela,et al.  Effect of physical training on insulin secretion and action in skeletal muscle and adipose tissue of first-degree relatives of type 2 diabetic patients. , 2010, American journal of physiology. Endocrinology and metabolism.

[5]  A. Vaag,et al.  Decreased insulin activation of glycogen synthase in skeletal muscles in young nonobese Caucasian first-degree relatives of patients with non-insulin-dependent diabetes mellitus. , 1992, The Journal of clinical investigation.

[6]  C. Kahn,et al.  Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle. , 2000, The Journal of clinical investigation.

[7]  G. Dailey,et al.  Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM. Evidence from studies in normal glucose-tolerant individuals with a first-degree NIDDM relative. , 1995, JAMA.

[8]  R. DeFronzo,et al.  Effect of fatty acids on glucose production and utilization in man. , 1983, The Journal of clinical investigation.

[9]  Kamran Nikbin,et al.  Validation of the K and J Parameters in a Compact Tension Specimen Containing Intergranular and Straight Crack Paths , 2010 .

[10]  G. Shulman,et al.  Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and β‐cell dysfunction , 2002, European journal of clinical investigation.

[11]  F. Hu,et al.  Primary prevention of diabetes: what can be done and how much can be prevented? , 2005, Annual review of public health.

[12]  D. Langin.  Control of fatty acid and glycerol release in adipose tissue lipolysis. , 2006, Comptes rendus biologies.

[13]  G. Shulman,et al.  Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional study. , 1997, Diabetes.

[14]  P. Jansson,et al.  Evidence for lactate production by human adipose tissue in vivo , 1990, Diabetologia.

[15]  J. A. Scarlett,et al.  Role of Glucose Transport in the Postreceptor Defect of Non-insulin-dependent Diabetes Mellitus , 1982, Diabetes.

[16]  Mark I McCarthy,et al.  Genome-wide association studies in type 2 diabetes , 2009, Current diabetes reports.

[17]  J. Bülow.  Measurement of adipose tissue blood flow. , 2001, Methods in molecular biology.

[18]  M. Nauck,et al.  A 25-year follow-up study of glucose tolerance in first-degree relatives of type 2 diabetic patients: association of impaired or diabetic glucose tolerance with other components of the metabolic syndrome , 2003, Acta Diabetologica.

[19]  J. Bülow,et al.  Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue. , 2000, American journal of physiology. Endocrinology and metabolism.

[20]  A. Vaag,et al.  Impaired endothelial function and insulin action in first-degree relatives of patients with type 2 diabetes mellitus. , 2009, Metabolism: clinical and experimental.

[21]  T. Valle,et al.  Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland Study design and 1-year interim report on the feasibility of the lifestyle intervention programme , 1999, Diabetologia.

[22]  P. Jansson,et al.  Glucose turnover and adipose tissue lipolysis are insulin-resistant in healthy relatives of type 2 diabetes patients: is cellular insulin resistance a secondary phenomenon? , 1999, Diabetes.

[23]  A. Vaag,et al.  Effect of 10 days of bedrest on metabolic and vascular insulin action: a study in individuals at risk for type 2 diabetes. , 2010, Journal of applied physiology.

[24]  J. Helge,et al.  Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects. , 2006, American journal of physiology. Endocrinology and metabolism.

[25]  N. Lassen,et al.  Blood flow through human adipose tissue determined with radioactive xenon. , 1966, Acta physiologica Scandinavica.

[26]  R. DeFronzo,et al.  Glucose clamp technique: a method for quantifying insulin secretion and resistance. , 1979, The American journal of physiology.

[27]  F. Assimacopoulos-Jeannet,et al.  Hyperinsulinemia increases the amount of GLUT4 mRNA in white adipose tissue and decreases that of muscles: a clue for increased fat depot and insulin resistance. , 1990, Endocrinology.

[28]  L. Strindberg,et al.  Validation of the 'internal reference technique' for calibrating microdialysis catheters in situ. , 1995, Acta physiologica Scandinavica.

[29]  L. Groop,et al.  Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. , 1989, The New England journal of medicine.

[30]  A. Vaag,et al.  Impact of 9 Days of Bed Rest on Hepatic and Peripheral Insulin Action, Insulin Secretion, and Whole-Body Lipolysis in Healthy Young Male Offspring of Patients With Type 2 Diabetes , 2009, Diabetes.