Abstract. The localization of insulin-like growth factor I (IGF-I, somatomedin C) was investigated in the kidney of adult rats during normal conditions and after nephrectomy, using immunocytochemical and biochemical methods. In the normal kidney, IGF-I immunoreactivity could be demonstrated mainly in cells in the medullary collecting ducts and in those parts of the thin limb of Henle's loop located in the outer medulla. During compensatory growth all parts of the collecting ducts, including those in the cortex, showed IGF-I immunoreactivity, as did cells in the entire thin limb of Henle's loop. No IGF-I immunoreactivity could be demonstrated in the proximal or distal tubules, either in the control kidney or during compensatory growth. Biochemical measurements showed a significantly higher content of IGF-I in the inner medulla than in the cortex in the normal kidney. Uninephrectomy resulted in significantly increased IGF-I content in the cortex. It is suggested that IGF-I is produced mainly in the collecting ducts and in the thin limb of Henle's loop and exerts its effect on other parts of the nephron by paracrine mechanisms.
Göran L. Andersson, Anna Skottner and Eva Jennische
Décio L Eizirik, Anna Skottner and Claes Hellerström
Eizirik DL, Skottner A, Hellerström C. Insulin-like growth factor I does not inhibit insulin secretion in adult human pancreatic islets in tissue culture. Eur J Endocrinol 1995;133:248–50. ISSN 0804–4643
Insulin-like growth factor I (IGF-I) has been found to increase insulin sensitivity and suppress insulin secretion, thereby having a potential interest as a therapeutic agent for non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present study was to investigate the direct actions of IGF-I (400 ng/ml) on human pancreatic islets, or on rat pancreatic islets, during a 48 h period in tissue culture. Insulin-like growth factor I did not affect medium insulin accumulation, DNA or insulin content or short-term glucose-induced insulin release of human islets. However, in rat islets the peptide induced a significant decrease in the insulin increase ratio in response to 16.7 mmol/l glucose. In conclusion, the present data suggest that IGF-I does not directly affect the function of human pancreatic β-cells If this in vitro data can be extrapolated to the in vivo situation, it suggests that the observed inhibitory effects of IGF-I on serum insulin levels may be secondary to peripheral effects of the peptide.
Décio L Eizirik, Department of Medical Cell Biology, Biomedicum, PO Box 571, S-751 23 Uppsala, Sweden
Karin E. Bornfeldt, Hans J. Arnqvist, Hans H. Dahlkvist, Anna Skottner and Jarl E. S. Wikberg
Abstract. Binding of IGF-I to plasma membranes from bovine mesenteric arteries was studied. The maximal specific binding of IGF-I was found to be 7.4 ± 1.7% of total 125I-IGF-I added to the incubation medium. Unlabelled IGF-I displaced 125I-IGF-I with an IC50 value of 0.5 nmol/l and a maximal displacement of 64.2 ± 2.8% of total binding. The potency of insulin to displace 125I-IGF-I was 100–1000-fold lower. Crosslinking of 125I-IGF-I to the receptor with disuccinimidyl suberate, followed by SDS-polyacrylamide gel electrophoresis under reducing conditions showed an IGF-I binding protein with a molecular weight of 146000 Dalton. In summary, we have shown the presence of receptors for IGF-I in plasma membranes isolated from macrovessels. The binding characteristics and the size of the binding unit were found to be similar to those of the IGF-1 receptor found in cultured vascular smooth muscle cells. Furthermore, insulin at high concentrations was found to interact with the IGF-I receptor.