The regulatory mechanism of insulin like growth factor secretion by high glucose in mesangial cell: involvement of cAMP

Heo, Jung-sun; Kang, Chang-won; Han, Ho-jae; Park, Soo-hyun

Korean Journal of Veterinary Research 2003;43(4):563-571.

Jung-sun Heo¹, Chang-won Kang¹, Ho-jae Han², Soo-hyun Park¹

¹Bio-safety Research Institute, College of Veterinary Medicine, Chonbuk National University
²College of Veterinary Medicine, Hormone Research Center, Chonnam National University

Mesangial 세포에서 고포도당에 의한 insulin-like growth factor의 분비조절기전에 관한 연구: cAMP와의 관련성

허정선¹, 강창원¹, 한호재², 박수현¹

¹전북대학교 수의과대학 생리학교실, 생체안전성 연구소
²전남대학교 수의과대학 생리학교실

Abstract

Dysfunction of mesangial cells has been contributed to the onset of diabetic nephropathy. Insulin like growth factors (IGFs) are also implicated in the pathogenesis of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I and IGF-II secretion in the mesangial cells. Furthermore, the relationship between cAMP and high glucose on the secretion of IGFs was not elucidated. Thus, we examined the mechanisms by which high glucose regulates secretion of IGFs in mesangial cells. Glucose increased IGF-I secretion in a time- (>8 hr) and dose- (>15 mM) dependent manner (p<0.05). Stimulatory effect of high glucose on IGF-I secretion is predominantly observed in 25 mM glucose (high glucose), while 25 mM glucose did not affect cell viability and lactate dehydrogenase release. High glucose also increased IGF-II secretion. The increase of IGF-I and IGF-II secretion is not mediated by osmotic effect, since mannitol and L-glucose did not affect IGF-I and IGF-II secretion. 8-Br-cAMP mimicked high glucose-induced secretion of IGF-I and IGF-II. High glucose-induced stimulation of IGF-I and IGF-II secretion was blocked not by pertussis toxin but by SQ 22536 (adenylate cyclase inhibitor). Rp-cAMP (cAMP antagonist), and myristoylated protein kinase A (PKA) inhibitor amide 14-22 (protein kinase A inhibitor). These results suggest that cAMP/PKA pathways independent of Gi protein may mediate high glucose-induced increase of IGF-I and IGF-II secretion in mesangial cells. Indeed, glucose (>15 mM glucose) increased cAMP formation. In conclusion, high glucose stimulates IGF-I and IGF-II secretion via cAMP/PKA pathway in mesangial cells.

Key Words: Diabetic nephropathy, Insulin-like growth factor, high glucose, cAMP, mesangial cell