Inhibitory Effect of Prednisone on Insulin Secretion in Man: Model for Duplication of Blood Glucose Concentration

Abstract

Treatment with oral prednisone (15 mg every 6 h) for 1 day plus a 4-h glucose infusion at 2.8 mg/min kg body weight to 5 normal, healthy individuals raised their blood glucose to 137 +/- 4.5 mg per 100 ml (mean +/- SEM). In order to evaluate the effects of steroid-induced hyperglycemia on insulin responses, a model for the duplication of blood glucose concentration in serial studies was developed. During glucose infusion at 5.7 mg/min kg body weight, the fractional uptake of glucose at the end of infusion (KG) was 2.08 +/- 0.2%/min and the apparent volume of distribution (V) was 285 +/- 10.5 ml/kg. Further increase in the rate of glucose infusion did not affect KG and V. Based on these parameters, KG and V, the stable blood glucose achieved during the prednisone study (C) was duplicated both after short (4 h) and prolonged (28 h) glucose infusions (138 +/- 4.5 and 146 +/- 4.5 mg/100 ml, respectively) at rates calculated as the product of KG.C.V. The effects of prednisone treatment on insulin secretion were examined (1) during fasting, (2) at identical glucose concentrations during glucose infusions at constant rates, and (3) in response to glucose pulse (0.1 g/kg) during the infusions. During fasting, there was a significant elevation of mean blood glucose with prednisone (99 +/- 1.8 mg/100 ml) compared with that in the control study (88 +/- 1.7 mg/100 ml). The plasma IRI, however, remained unchanged (10 +/- 2.3 vs 10 +/- 1.6 muU/ml). During glucose infusions in the presence of similar blood glucose levels, the IRI was lower after prednisone treatment (18 +/- 1.5 muU/ml) than during the short and prolonged glucose infusions (42 +/- 5.1 and 63 +/- 7.0 muU/ml). The insulin response to the glucose pulse also was significantly lower during steroid treatment. Thus, prednisone apparently has an early inhibitory effect on the insulin response to glucose.

Functional and Molecular Aspects of Glucocorticoids in the Endocrine Pancreas and Glucose Homeostasis

“…In the latter, glucose intolerance was also a result of decreased glucose clearance; while no differences in endogenous glucose production was observed too (Schneiter & Tappy, 1998). Although the literature concerning rapid GC effects on insulin secretion in healthy individuals is scarce, it seems that insulin secretion under glucose infusion is reduced (Shamoon et al, 1980) or unaltered (Schneiter & Tappy, 1998) in response to a glucose challenge, suggesting an acute inhibitory effect of the GCs on -cells (Kalhan & Adam, 1975). It should also be mentioned that adaptive compensation to short GC exposures are transitory and usually reversible after discontinuation of steroid treatment (van Raalte et al, 2010).…”

“…The acute effects of GCs in healthy individuals, as judged by cortisol infusion (Shamoon et al, 1980) or by high doses of prednisolone (Kalhan & Adam, 1975;van Raalte et al, 2010), seem to be inhibitory for insulin secretion. This is based on the fact that circulating insulin levels during fasting state are not altered following GC treatment, despite the increase in blood glucose levels.…”

Glikokortykosteroidy a zaburzenia metabolizmu glukozy

“…Glikokortykosteroidy wpływają na funkcje komórek beta i alfa wysp Langerhansa. W ostatnich latach wykazano, że hiperglikemia wywołana przez GS jest konsekwencją nie tylko insulinooporności, ale również istotnego zaburzenia funkcji komórek wysp trzustkowych [41,42]. Hormony te upośledzają zdolności sekrecyjne komórki beta.…”

“…Ponadto GS wydają się promować apoptozę komórek beta [45]. Zarówno w badaniach in vitro, jak i in vivo, zarówno na modelu zwierzęcym, jak i na modelu ludzkim wykazano, że jednorazowa duża dawka hormonu steroidowego (hydrokortyzon lub prednizolon) zmniejsza istotnie sekrecję insuliny [41,46,47]. Jednak w wyniku długotrwałego podawania GS upośledzenie czynności komórek beta może być maskowane w pewnym stopniu przez hiperinsulinemię, kompensującą obwodową insulinooporność [42].…”

Gene and Cell-Replacement Therapy in the Treatment of Type 1 Diabetes

“…These agents produce insulin resistance de novo (56) and at the same time decrease islet endocrine function (57,58). In many instances, the ␤-cell is incapable of increasing insulin release sufficiently in response to such insulin resistance, and hyperglycemia ensues.…”