Insulin secretion by pancreatic B-cells during pregnancy and the perinatal period of life. Participation of prolactin and insulin signaling cascades in the secretory process and alterations induced by protein malnutrition and disturbances of lipid metabolism

Abstract

Diabetes mellitus (DM) is defined as a syndrome of persistent hyperglycemia resulting from the lack of insulin production generally associated to increased resistance to the hormone. DM is classified in: 1) Insulin dependent diabetes mellitus (IDDM) or type 1 diabetes; 2) Non insulin dependent diabetes mellitus (NIDDM) or type 2 diabetes; 3) Diabetes mellitus associated to other illness, or secondary diabetes mellitus, and 4) Gestational diabetes mellitus. Almost 90% of diabetic patients belong to the type 2. This is an endocrine disorder characterized by multiple defects in insulin action and insulin secretion, and results from an increase in insulin resistance associated with the incapacity of the endocrine pancreas to secrete increasing amount of insulin to compensate hyperglycemia. However, only recent1y it was realized that the inability of β cell to secrete adequate quantities of insulin is really important in the onset of the disease. It is now accepted that the maintenance of a β cell mass and turnover throughout life is critical for the maintenance of normoglycemia. The perinatal period of life is crucial for the growing and differentiation of the endocrine pancreas. Inadequate formation of the islets of Langerhans, for example provoked by protein malnutrition during this period may cause diabetes later in life. Also during pregnancy, there is an increase in insulin resistance accompanied by an increase of β cells mass and glucose sensitivity. These alterations are orchestrated by different hormones especially placental lactogens and prolactin. In this project we will study the mechanism of insulin secretion during these two periods of life. We will analyzed the prolactin and insulin signaling pathways in β cells, and the alterations caused by protein malnutrition and hyperlipidemia on the mechanism of insulin secretion. (AU)