HIGH-FAT DIET-INDUCED HYPERGLYCEMIA - PREVENTION BY LOW-LEVEL EXPRESSION OF A GLUCOSE-TRANSPORTER (GLUT4) MINIGENE IN TRANSGENIC MICE

High-fat intake leading to obesity contributes to the development of n on-insulin-dependent diabetes mellitus (NIDDM, type 2). Similarly, mic e fed a high-fat (safflower oil) diet develop defective glycemic contr ol, hyperglycemia, and obesity, To assess the effect of a modest incre ase in the expression of GLUT4 (the insulin-responsive glucose transpo rter) on impaired glycemic control caused by fat feeding, transgenic m ice harboring a GLUT4 minigene were fed a high-fat diet. Low-level tis sue-specific (heart, skeletal muscle, and adipose tissue) expression o f the GLUT4 minigene in transgenic mice prevented the impairment of gl ycemic control and accompanying hyperglycemia, but not obesity, caused by fat feeding. Thus, a small increase (less than or equal to 2-fold) in the tissue level of GLUT4 prevents a primary symptom of the diabet ic state in a mouse model, suggesting a possible target for interventi on in the treatment of NIDDM.