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ABSTRACT
Islet amyloid polypeptide (IAPP) is a 37 amino acid peptide present in pancreatic β-cells. Pancreatic and circulating IAPP concentrations in rat models of diabetes were measured using a specific radioimmunoassay. Pancreatic IAPP-like immunoreactivity (IAPP-IR) in dexamethasone-treated rats was twice that of the control rats (1571±137 vs 657±176 (s.e.m.; n= 6) pmol/g), and this was reflected by similar changes in the plasma IAPP-IR (272±17 vs 102±10 pmol/l). In streptozotocin-treated rats, pancreatic IAPP-IR (200±90 pmol/g) was reduced compared with controls. There was a significant positive correlation between pancreatic and plasma IAPP-IR and insulin, with r values of 0·82 and 0·91 for the plasma and pancreas respectively. Characterization of pancreatic immunoreactivity, using gel chromatography, revealed two peaks of IAPP-IR, one which coeluted with synthetic human amidated IAPP and another peak, presumably a fragment or breakdown product, which eluted later. Chromatography of the plasma IAPP-IR revealed that >90% of the IAPP-IR eluted in the void volume, although the remaining IR coeluted with the synthetic IAPP standard. These results are not straightforwardly compatible with the suggested role for IAPP as a hormonal, paracrine or autocrine inhibitory regulator of insulin secretion in the maintenance of carbohydrate homeostasis.
Journal of Endocrinology (1990) 126, 425–429
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ABSTRACT
The factors associated with high concentrations of circulating plasma immunoreactive endothelin in patients with diabetes mellitus are unknown. Plasma and tissue (lung and kidney) immunoreactive endothelin levels were therefore measured by radioimmunoassay in three animal models of diabetes mellitus: dexamethasone-treated rats (2 mg/kg per day for 12 days), streptozotocin-treated rats (100 mg/kg, 4 days before being killed) and rats treated with both dexamethasone and streptozotocin. Plasma concentrations of immunoreactive endothelin in the dexamethasone-treated rats (3·13±0·28 pmol/l, mean ± s.e.m., n = 15) were significantly (P < 0·005) higher than those in controls (1·33±0·18 pmol/l, n = 15), while plasma concentrations of immunoreactive endothelin in streptozotocin-treated rats (n = 8) and rats treated with both dexamethasone and streptozotocin (n= 14) were undetectable (< 0·5 pmol/l). Fast protein liquid chromatographic analysis of the plasma immunoreactive endothelin of dexamethasone-treated rats showed four peaks: one in the void volume, one eluting before endothelin-3, one eluting after endothelin-3 and before endothelin-1 and one eluting in a position identical with that of endothelin-1. Pulmonary concentrations of immunoreactive endothelin in the three groups of rats with diabetes mellitus were lower (P < 0·005) but no significant change was found in renal immunoreactive endothelin. These findings indicate that short-term dexamethasone treatment increases plasma levels of immunoreactive endothelin while streptozotocin treatment decreases them. Thus, multiple factors may influence plasma concentrations of immunoreactive endothelin in diabetes mellitus.
Journal of Endocrinology (1991) 130, 123–127
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ABSTRACT
Advances in techniques in molecular biology have facilitated the research into endogenous opioids and related peptides in several ways. The organization and expression of genes and the primary structure of three precursor proteins of opioid peptides have been elucidated. These studies predicted the presence of potentially bioactive peptides, which has been confirmed by later studies. Advances in techniques in protein chemistry have helped to elucidate the distribution and molecular forms of endogenous opioids and related peptides in the body, and the processing of precursor proteins. Studies on the function of these peptides have shown a broad spectrum of actions. Leumorphin, a newly identified peptide, has been shown to exhibit unique biological activities. In spite of extensive studies, the physiological and pathophysiological significance of opioid peptide systems are not yet completely understood. This is mainly due to the paucity of our knowledge about opioid receptors. Further studies on the subtypes of opioid receptors will help to elucidate all aspects of the function of endogenous opioids and related peptides.
J. Endocr. (1985) 107, 147–157
