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EVALUATION OF THE MODULATORY EFFECT OF METHANOLIC EXTRACT OF CADABA FARINOSA Forssk ON CARBONIC ANHYDRASE IN STREPTOZOTOCIN INDUCED DIABETIC RATS
CHAPTER ONE
1.0 INTRODUCTION
Diabetes mellitus is a metabolic disorder of impaired glucose regulation, characterized by persistent hyperglycemia. Hyperglycemia has been associated with increased morbidity and mortality in diabetic subjects. The development of long-term complications in diabetes is influenced by hyperglycemia. Poor control of hyperglycemia accelerates progression of diabetic complication.
Hyperglycemia, the major defining feature of all forms of diabetes, arises due to absolute or relative insulin deficiency, increased hepatic glucose production (HGP), due to increased hepatic lactate uptake produced by glycolytic cells. It has been reported that the plasma glucose level is maintained by regulation of HGP and glucose uptake in the peripheral tissues (DeFronzo and Ferrannini, 1987; Cherrington et al., 1987). Moreover, fasting plasma glucose level has been shown to be directly correlated with the rate of fasting hepatic glucose production (Bogardus et al., 1984; Firth et al., 1987). Thus, the increase in hepatic glucose production in type 2 diabetes may be due to increased supply of gluconeogenic precursor (lactate) for increase gluconeogenesis. Previous studies have found that increased rates of glucose lactate interconversion termed cori cycle have been observed in diabetic dogs (Stevenson et al., 1983). Zawadzki et al. (1988) concluded that the rates of endogenous glucose production and that of Cori cycle are increased in subjects with type 2 diabetes. These showed that, increased provision of lactate is of considerable importance for increased hepatic glucose production in type 2 diabetes.
Diabetes is being combated through aggressive treatment directed at lowering circulating blood glucose and inhibiting postprandial hyperglycemic rise mainly by stimulating pancreatic β-cells to secret more insulin, increasing insulin receptor sensitivity, inhibiting hepatic glucose production and also enhancing glucoseuptake by glucose utilizing tissues. Current strategies to treat diabetes include reducing insulin resistance using glitazones (or thiozolidinediones) which are insulin sensitizers, supplementing insulin supplies with exogenous insulin, increasing endogenous insulin production with oral hypoglycemic such as sulfonylureas and meglitinides, reducing hepatic glucose production through biguanides, and limiting postprandial glucose absorption with alpha-glucosidase inhibitors.sa
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