Obesity and diabetes are increasingly significant health care concerns. Type 2 diabetes (T2D), characterized by target tissue resistance to insulin and impaired pancreatic b-cell insulin secretion, affects 5-10% of the adult population. The amount of adipose tissue is highly correlated with and may contribute to insulin resistance. Obesity affects over 20% of the population and more than 80% of type 2 diabetics are obese, suggesting that obesity may be of pathophysiological importance to subjects genetically prone to develop diabetes. Multiple lines of evidence have suggested an endocrine role of adipose tissue to modulate energy homeostasis and insulin sensitivity, other studies suggest the possibility of a dynamic """"""""cross-talk"""""""" relationship between muscle and fat. As skeletal muscle is the principal tissue of insulin mediated glucose disposal and the major site of peripheral insulin resistance in type 2 diabetics, these data give rise to the hypothesis that adipocyte endocrine dysfunction can result in glucose intolerance and insulin resistance in skeletal muscle. The long-term goal of this proposed study is to understand the communication between fat and muscle tissue in T2D. This study aims to determine 1) if fat from diabetic subjects contributes to the development of insulin resistance in skeletal muscle, and 2) if metabolic disturbances present in skeletal muscle from diabetic subjects alters the metabolic behavior of adipose tissue. Specifically we will use adipose and skeletal muscle biopsy tissue and cultured cells from diabetic and control subjects to ask: 1) what is the metabolic behavior of isolated adipocytes or myocytes in culture and how is it altered when their physiologic proximity is restored in culture? 2) What is the effect of T2D on the metabolic behavior of these tissues and is fat-muscle communication altered when proximity is re-established in culture? 3) Can treatment of either tissue alone with anti-diabetic thiazolidinediones alter the nature of the communication between these tissues when their physiologic relationship is restored in culture? Studying fat-muscle communication will enhance our understanding of the molecular mechanisms underlying obesity-diabetes syndromes, and may suggest new treatment strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08DK061987-01
Application #
6508156
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2002-08-01
Project End
2007-06-30
Budget Start
2002-08-01
Budget End
2003-06-30
Support Year
1
Fiscal Year
2002
Total Cost
$121,770
Indirect Cost
Name
University of California San Diego
Department
Pediatrics
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Phillips, Susan A; Kung, Jacqueline; Ciaraldi, Theodore P et al. (2009) Selective regulation of cellular and secreted multimeric adiponectin by antidiabetic therapies in humans. Am J Physiol Endocrinol Metab 297:E767-73
Phillips, Susan A; Ciaraldi, Theodore P; Oh, Deborah K et al. (2008) Adiponectin secretion and response to pioglitazone is depot dependent in cultured human adipose tissue. Am J Physiol Endocrinol Metab 295:E842-50
Phillips, Susan A; Choe, Charles C; Ciaraldi, Theodore P et al. (2005) Adipocyte differentiation-related protein in human skeletal muscle: relationship to insulin sensitivity. Obes Res 13:1321-9
Ciaraldi, Theodore P; Phillips, Susan A; Carter, Leslie et al. (2005) Effects of the rapid-acting insulin analog glulisine on cultured human skeletal muscle cells: comparisons with insulin and insulin-like growth factor I. J Clin Endocrinol Metab 90:5551-8
Phillips, Susan A; Ciaraldi, Theodore P; Kong, Alice P S et al. (2003) Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy. Diabetes 52:667-74
Chandran, Manju; Phillips, Susan A; Ciaraldi, Theodore et al. (2003) Adiponectin: more than just another fat cell hormone? Diabetes Care 26:2442-50