THE EFFECT OF RECOMBINANT HUMAN GROWTH-HORMONE ON REGULATION OF GROWTH-HORMONE SECRETION AND BLOOD-GLUCOSE IN INSULIN-DEPENDENT DIABETES

GH hypersecretion in insulin-dependent diabetes (IDDM) is well documen ted. Although it has recently been shown that residual insulin secreti on determines the magnitude of this GH hypersecretion, the underlying mechanisms of the disorder have not yet been clarified. The 24-h GH an d blood glucose profiles, insulin-like growth factor I (IGF-I) concent rations and GH responses to GRF were analyzed in 21 insulin-dependent diabetics and 4 healthy subjects be.ore and after 7 days treatment wit h recombinant human GH (rhGH) (4 IU given sc at 0800 h). According to C-peptide response to glucagon IDDM patients were subdivided into C-pe ptide negative (CpN, n = 12) patients without endogenous pancreatic be ta-cell activity and C-peptide positive (CpP, n = 9) patients with end ogenous insulin secretion. No significant difference could be observed between the mean 24-h blood glucose profile before and after rhGH tre atment in any treated group. Before and on rhGH treatment the highest 24-h GH values were observed in CpN patients when compared to CpP and controls. The rhGH treatment induced a similar increase in the mean 24 -h GH concentrations in all groups studied which was statistically sig nificant only in CpP diabetics. Mean pretreatment serum IGF-I concentr ations were not significantly different between CpN, CpP patients and controls. The net increase in IGF-I concentrations after rhGH treatmen t was however, significantly lower in CpN patients than in CpP and con trol subjects. GRF - induced GH response before and after rhGH treatme nt was significantly greater in diabetics than in controls. The respon se of GH to GRF in CpN diabetics was however, almost unchanged after t reatment whereas it became lower in CpP diabetics and controls. The do se of 4 IU of rhGH increased significantly GH levels in diabetics with preserved beta-cell function with consequent increase in IGF-I levels and attenuation of GRF induced GH response. In contrast, the same dos e of rhGH failed to induce significant increase in GH levels in diabet ics without residual beta-cell activity, most probably due to already high pretreatment levels. In addition, neither increase in IGF-I level s nor suppression of GH response to GRF on rhGH treatment was observed in CpN diabetics. The results are in keeping with an important role o f portal insulin in GH-induced hepatic IGF-I secretion.