Coupling mechanisms of insulin secretion - roles of mitochondrial metabolism and cAMP.
Summary, in English
The aim of this thesis was to investigate the mechanisms of insulin secretion, and especially what couples glucose stimulation of the beta-cell to insulin secretion.
We have found that anaplerosis via pyruvate carboxylase is essential for both phases of glucose-stimulated insulin secretion, presumably via generation of an increased ATP/ADP ratio. Further, we discovered that expression of PDK1 is upregulated in INS-1 832/13 cells cultured at high concentrations of glucose, and that knock-down of PDK1 enhances insulin secretion. Both these findings prove that mitochondrial metabolism is important for insulin secretion, and points to the involvement of pyruvate cycling. We have also showed that PKA signaling is stimulated by glucose, and that inhibition of PKA decreases glucose-stimulated insulin secretion in INS-1 832/13 cells.
- Basic Medicine
- secreting systems
- pyruvate dehydrogenase kinase
- pyruvate carboxylase
- Diabetes - Islet Patophysiology
- Hindrik Mulder
- ISBN: 91-85559-67-9
15 December 2006
Segerfalkssalen, Wallenberg neurocentrum, Sölvegatan 17
- Claes Wollheim (professor)