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	INTRODUCTION
	PANCREATIC β-CELLS
	Pathophysiology and Phases of Hyperglycemia-induced β-cell Dysfunction:
	Lipotoxicity:
	Genetic Contributions
	Time course of β- cell glucose toxicity:
	PERIPHERAL INSULIN TARGET TISSUES
	CELLULAR AND MOLECULAR MECHANISMS OF GLUCOSE TOXICITY
	Pancreatic β-cells:
	Peripheral Insulin Target Tissues
	Microvascular and other complications:
	CLINICAL IMPLICATIONS