Effects of galanin on insulin and glucagon secretion in the rat

Galanin-like immunoreactivity has been visualized in nerve fibers in the islets of Langerhans, suggesting an involvement of galanin in the neural regulation of islet function. In this study, we investigated the effects of galanin on basal and stimulated insulin and glucagon secretion by infusing the peptide at three different dose rates in rats. We also studied the direct effect of galanin on insulin secretion from freshly isolated rat islets. At 320 pmol/kg/min, but not at 20 or 80 pmol/kg/min, galanin lowered basal plasma insulin levels. In contrast, basal plasma glucagon levels were lowered by galanin already at 20 and 80 pmol/kg/min. Furthermore, galanin inhibited both glucose- and arginine-induced insulin release at all three dose levels, whereas arginine-induced glucagon release was not affected by galanin. Glucose-stimulated insulin secretion from isolated rat islets was dose-dependently suppressed by galanin (10^-6-10^-8M). Therefore, it is concluded that galanin in rats inhibits insulin secretion, both in vivo and in vitro, and that at lower dose levels, the peptide also inhibits basal glucagon release.     

Classification of Diabetes Mellitus by Studies of C-Peptide Secretory Capacity

Residual pancreatic B-cell function was investigated in children with diabetes mellitus in whom classification of the type of disease was difficult at the first visit. Intravenous glucagon tests were performed at the first visit and subsequently, the C-peptide responses compared. Based on our data on a limited number of patients, we propose C-peptide concentrations of 3.0 to 3.5 ng/ml at the peak or at 6 min after injection of glucagon, as the critical level which distinguishes non-insulin dependent from insulin-dependent diabetes mellitus. However, the degree of obesity, clinical stage and other factors also need to be considered in the classification of diabetes mellitus.     

肥胖患者胰升糖素水平变化及其对空腹血糖的影响

目的　探讨肥胖患者胰升糖素的变化特点及其对血糖的影响。方法　将 82例患者根据体重指数分为 3组 :A组 (BMI <2 4,n =2 3 )、B组 (2 4≤BMI <2 7,n =2 7)、C组 (BMI≥ 2 7,n =3 2 ) ,分别测定胰升糖素、胰岛素、空腹血糖 ,采用单因素方差分析法与Spearman等级相关性分析法进行分析。结果　 3组胰升糖素分别为 (15 6.3± 5 8.6)、(186.7± 67.5 )、(2 2 2 .2± 88.4)ng·L-1,C组与A组比较有显著性差异 (P <0 .0 1) ;3组胰岛素分别为 (15 .4± 4.7)mIU·L-1、(2 0 .6± 9.6)mIU·L-1、(2 2 .3± 10 .6)mIU·L-1,B组、C组与A组比较差异有显著意义 (P <0 .0 5、P <0 .0 1) ;B、C两组胰升糖素与空腹血糖呈正相关。结论　肥胖患者胰岛素、胰升糖素一致性增高 ,胰升糖素的增高是空腹血糖增高的重要因素。     

大鼠应激性溃疡与胃泌素、胰高血糖素和生长抑素的相关性研究

采用冷束缚法建立大鼠应激性溃疡模型，以探讨胃肠激素与应激性溃疡发病的相关性。实验组置于（４±２）℃环境，３Ｈ，对照组置于（１８±３）℃，３ｈ，分别检测不同时间血清胃泌素、胰高血糖素、生长抑素的水平。结果表明，实验组胃泌素、胰高血糖素水平明显高于对照组，生长抑素水平明显低于对照组。提示胃泌素、胰高血糖素、生长抑素可能从不同的角度参与了应激性溃疡的消长过程。     

Structure-activity studies of hydrophobic amino acid replacements at positions 9, 11 and 16 of glucagon

We have designed and synthesized eight compounds 2-9 which incorporate neutral, hydrophobic amino acid residues in positions 9, 11 and 16 of the glucagon molecule: (2) [desHis¹,Va1⁹,11e^11,16] glucagon amide, (3) [desHis¹,Val^9,11,16]glucagon amide, (4) [desHis¹,Va1⁹,Leu^11,16]glucagon amide, (5) [desHis¹,Nle⁹,11e^11,16]glucagon amide, (6) [desHis¹,Nle⁹,Val^11,16]glucagon amide, (7) [desHis¹,Nle⁹,Leu^11,16]glucagon amide, (8) [desHis¹,Val⁹,Leu^11,16,Lys^17,18,Glu²¹]glucagon amide and (9) [desHis¹,Nle⁹,Leu^11,16,Lys^17,18,Glu²¹]glucagon amide. The effect of neutral, hydrophobic residues at positions 9, 11 and 16 led to good binding to the glucagon receptor. Compared to glucagon (IC₅₀= 1.5 nM), analogues 2-9 were found to have IC₅₀ values of 6.0, 6.0, 11.0, 9.0, 2.5, 2.8, 6.5 and 7.0 nM, respectively. When these compounds were tested for their ability to block adenylate cyclase (AC) activity, they were found to be antagonists having no stimulation of adenyl cyclase, with PA₂, values of 6.15, 6.20, 6.30, 7.25, 6.10, 7.30, 6.25 and 7.25, respectively. © Munksgaard 1997.     

Alteration in plasma glucose levels in Japanese encephalitis patients

A unique factor, human T cell hypoglycaemic factor (hTCHF), has been shown to produce hypoglycaemia during the convalescent stage in the plasma of patients with Japanese encephalitis virus (JEV) infection. The present study was undertaken to investigate the ability of T cells from fresh peripheral blood mononuclear cells (PBMC) of such patients to produce hTCHF. The PBMC, as well as the individual subpopulations, were cultured for 24 h and the culture supernatants (CS) were assayed for hypoglycaemic activity. The activity was observed in the CD8+ T cells. The hypoglycaemia in JE-confirmed patients coincided with the gradual rise in circulating glucagon level, with no significant alterations in insulin, growth hormone and cortisol levels. The hTCHF was purified by ion exchange chromatography and the purified protein was observed as a approximately 25 kDa band on SDS-PAGE. Secretory hTCHF in the sera of patients and T cell CS was present in 88% of convalescent serum samples. We conclude that during the convalescent stage of JEV infection, a unique factor, hTCHF, is secreted by activated CD8+ T cells from patients and that this is responsible for the development of hypoglycaemia.     

Glucagon-induced somatostatin release from perifused rat hypothalamus: calcium dependency and effect of cysteamine treatment

Somatostatin (SRIF) release from rat hypothalamus was investigated in vitro with a perifusion system. Glucagon (1 microM) and high potassium concentrations (56 mM) stimulated SRIF release in a calcium-dependent manner. Pretreatment of the rat with cysteamine (30 mg/100 g body weight, 7 h earlier) significantly reduced SRIF release from the hypothalamus in glucagon- and high potassium-stimulated states as well as in the basal state. SRIF release from rat hypothalamus was also stimulated by both dibutyryl cyclic AMP (1 mM) and theophylline (3 mM). These results suggest that glucagon, acting in a calcium-dependent manner and possibly through the adenylate cyclase-cyclic AMP system, stimulates SRIF release from rat hypothalamus and that cysteamine treatment reduces releasable SRIF in the hypothalamus.     

Effects of the C-terminal Peptide of the αs subunit of the G protein on the regulation of Adenylyl Cyclase and Protein Kinase A activities by Biogenic Amines and Glucagon in Mollusk and Rat Muscles

The C-terminal parts of the subunits of heteromeric G proteins play an important role in the functional linkage of G proteins with receptors of the serpentine type. The present report describes studies of the effects of the C-terminal octapeptide 387–394 of the _s subunit of the mammalian G protein on the transmission of the hormonal signal via the hormone-sensitive adenylyl cyclase signal system, whose major components are receptors of the serpentine type, G proteins, and the enzymes adenylyl cyclase and protein kinase A. The peptide synthesized here, 387–394 amide (10^–7 - 10^–4 M), dose-dependently decreased adenylyl cyclase and protein kinase A activities stimulated by serotonin and glucagon in smooth muscle from the freshwater bivalve mollusk Anodonta cygnea and by the agonist isoproterenol in rat skeletal muscle. At a concentration as low as 10^–7 M, the peptide released potentiation of the stimulatory effects of hormones on adenylyl cyclase activity due to the non-hydrolyzable guanine nucleotide analog Gpp[NH]p. At the same time, it had almost no effect on the stimulation of adenylyl cyclase activity by non-hormonal agents (NaF, Gpp[NH]p, and forskolin). The inhibitory effects of hormones on adenylyl cyclase and protein kinase A activities persisted in the presence of the peptide. Our data demonstrate the importance of the C-terminal part of the _s subunit of the stimulatory G protein for its functional linkage with receptors of the serpentine type and throw light on the molecular mechanisms of the interactions between G proteins and receptors.Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 89, No. 7, pp. 837–850, July, 2003.     

Pancreatic endocrine cells in Bufo bufo: immunocytochemistry and ultrastructure

The endocrine pancreas of the toad consists of rounded islets of various sizes embedded in the exocrine tissue. Isolated cells are also present. At least 4 types of endocrine cell are distinguishable by shape, size and electrondensity of the secretory granules as well as by their immunoreactivity with different antisera: insulin, somatostatin, pancreatic polypeptide, and glucagon cells. Insulin cells can be divided into 2 types according to their cytoplasmic electrondensity. Colocalisation of different hormones in the same cell is rarely observed. The close contact between endocrine and exocrine cells and the scarcity of nerve supply is indicative of a paracrine control of hormone secretion.