Hormonal parameters during the last trimester of pregnancy contribute to a natural increase of insulin resistance. It is not known whether any of these are further involved in the manifestation of gestational diabetes mellitus (GDM) in affected individuals. Basal levels of adrenocorticotropic hormone, cortisol, growth hormone, insulin-like growth factor-I, prolactin, glucagon, estradiol, progesterone, human placental lactogen and human chorionic gonadotropin were investigated in 15 nonobese women with GDM and 26 matched normal pregnant women (N). A linear discriminant analysis was performed to further compare the predictive value of the basal hormone levels. Plasma glucagon levels were significantly higher in the GDM group (p = 0.014); this difference was even higher (p = 0.007) when the number of women was increased (GDM = 33, N = 62). No significant differences were found in the levels of any of the other hormones. It is not clear whether elevated glucagon levels have any involvement in the pathogenesis of GDM or simply reflect the relative insulin deficiency of these women.
The aim of the present study was to examine fasting (0') and postglucose glucagon levels in normal and gestational diabetes mellitus (GDM) pregnancy, as available data are somewhat conflicting. To this end we studied 18 women with GDM at 26-32 weeks of pregnancy and compared these with 26 normal pregnant women matched for age and BMI. We also examined glucagon suppressibility postpartum (2-4 months) in the same ex-GDM women, in whom normal glucose tolerance was confirmed (WHO criteria) and compared these with 17 controls matched for age and BMI. Glucose, insulin and glucagon levels were measured during a 100 or 75 g oral glucose tolerance test (OGTT) respectively. In pregnant women, baseline and 3 h after glucose ingestion, plasma glucagon levels were significantly higher (p < 0.05) in women with GDM compared to normal women. Interestingly, in normal pregnancy a significant increase (p < 0.01) of postglucose plasma glucagon levels at 1 and 2 h compared to baseline levels was observed, while there was no change in GDM pregnancy. In postpartum euglycaemic women, there was no difference in basal glucagon levels between the two groups. A differential glucagon response during OGTT was observed: in control women there was a significant glucagon suppression (p < 0.01) at 2 h, while there was a significant glucagon increase (p < 0.01) 1 h after glucose ingestion, in ex-GDM women. We conclude that (a) absence of the suppressibility of glucagon in ex-GDM women with normal OGTT may indicate insulin resistance and might be involved in the natural history towards glucose intolerance; and (b) nonsuppression of glucagon in normal late pregnancy as well as in pregnancy complicated by GDM may be due to "physiological" insulin resistance of the alpha cells during this period.
SummaryTo assess the effect of naturally-present amylin in the control of insulin release we infused a novel amylin antagonist, its 8-37 fragment, or amylin in anaesthetized rats for 60 min, and 30 min after the start arginine was infused for 14 min. Amylins_3v decreased the blood glucose concentration by 18 % whereas the plasma insulin concentration was 90 % higher following arginine treatment. In contrast amylin infusion raised both glucose and insulin concentrations. These results suggest that while amylin added at high dose can induce peripheral insulin resistance, naturally present amylin tonally controls insulin secretion. [Diabetologia (1994) 37: 436-438] Key words Amylin physiology, insulin secretion, amylin antagonists, islet paracrine physiology.Amylin (islet amyloid polypeptide) is a 37-amino acid polypeptide synthesised in the islet beta cell [1]. Circulating plasma concentrations are of the order 2-20 pmol/1, whereas systemic biological actions of the peptide are evident at nanomolar concentrations [2,3]. Reported extra-islet effects of amylin infusion in animals may represent 'cross-talk' at receptors for the homologous peptides CGRP and calcitonin [4]. As amylin is secreted from the beta cell into an islet portal circulation [5], the local intra-islet concentrations are greater than in the peripheral circulation. This may be sufficient to blunt insulin secretion, an effect demonstrated to occur at a plasma concentration of approximately 2 nmol/1 in human subjects [6] and at 75 pmol/1 in isolated perfused rat pancreas [7].The development of competitive antagonists of amylin may provide a tool to separate its physiologic from pharmacologic actions. [4], and inhibits the effects of added amylin to depress insulin secretion and increases insulin secretion from perifused, isolated rat islets [8]. CORPs_37 has been shown to enhance arginine-stimulated insulin secretion from anaesthetized rats [9], although it is not clear if this peptide antagonist predominately acts by attenuating CGRP effects or amylin effects in the islet. We have therefore tested whether amylin8 37 could enhance insulin secretion in rats in vivo. Materials and methods Animals and treatmentMale Wistar rats (200-250 g, n = 27) were obtained from Bantin and Kingman (Hull, UK) and maintained on rat feed ad libitum. They were fasted from 16.00 hours on the day prior to study. On the study day general anaesthesia was induced with an intraperitoneal injection of 0.7 ml of an aqueous mixture of 1.25 mg/ml midazolam (Hypnovel, Roche, Welwyn Garden City, UK), 91 ~tg/ml fentanyl citrate and 2.5 mg/ml fluanisone (Hypnorm, Janssen, Oxford, UK), and maintained with further 0.25 ml doses. Cannulae (0.63 mm outer diameter; Portex, Hythe, UK) were placed in a femoral vein for infusion of test substances and in a femoral artery for blood sampling, and were kept patent with flushes of 0.9 % NaC1 (saline) containing 50 units/ml heparin. At time 0 min a primed, continuous infusion of amylins_37 or amylin
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