Insulin-producing b-cells and glucagon-producing a-cells play a central role in glucose homeostasis (1). These cells are directly and inversely regulated by D-glucose, by mechanisms involving uptake and metabolism of the sugart. Our laboratory studies the molecular and cellular biology of pancreatic glucose sensing. Previous results have contributed to the hypothesis that the expression level of glucokinase in a- en b- cells determines (in part) the functioning of the sensor (2-4), both in rats (2,3) and in man (4). In addition to that, G-protein coupled receptors in b-cells modulate via regulated cAMP production the amplitude of the effector part of the glucose sensor ( 1,5). The present project focuses on one aspect of glucose sensing, namely the hypothesis that cytoplasmic NADPH is a candidate signaling molecule, coupling metabolism and cell function (6). The project starts by validating two in vitro models, MIN6 and INS-1 b-cells, which are known from the literature to be glucose-responsive (7,8). We will first measure "anaplerosis" and glucoseinduced function in these cells. Subsequently, the cellular [NADPH]/[NADP+] and [NADP]/[NAD+] ratios (both mitochondrial as cytoplasmic) will be measured. The project aims to be multidisciplinary, comprising biochemical, molecular, cell biological and physiological techniques; other aspects of the study of the sensor are supported by funds from the FWO (awarded) IUAP (awarded) and the EC (pending).
|Effective start/end date||1/01/97 → 31/12/98|
Flemish discipline codes
- Biological sciences