Experimental models for the study of diabetogenesis in laboratory animals

The normal process of glucose-induced insulin release involves three major steps. First, glucose is identified by the pancreatic B-cell as an insulinotropic factor. Second, calcium accumulation in a critical cellular site triggers the release process. Third, a microtubular-microfilamentous system serves as the effector system for the translocation and eventual extrusion of secretory granules. It is possible to interfere rather specifically with each of these events. For instance, fasting results in an impairment of the process of glucose identification. Various pharmacological agents, including organic calcium-antagonists may uncouple the metabolic process of glucose recognition form the effector response. Last, experimental alterations of the B-cell microtubular-microfilamentous system cause severe disturbances in the dynamics of insulin release. It is proposed that such experimental models may help to elucidate the primary lesion in different types of spontaneous diabetes mellitus in laboratory animals.