Galanin of the homologous species inhibits insulin secretion in the rat and in the pig.

It is known that pig galanin inhibits insulin secretion in dogs, rats and mice. The present study examined whether species-specific, homologous, galanin inhibits insulin secretion. Thus, the effects of rat galanin were examined in the rat, and the effects of pig galanin were examined in the pig, both in vivo and in vitro. In conscious rats, synthetic rat galanin (2 nmol kg-1) abolished the glucose- (0.56 mmol kg-1) induced increase in plasma insulin levels. In vitro, rat galanin (10(-9) to 10(-6) mol l-1) inhibited glucose- (8.3 mmol l-1) stimulated insulin release from isolated rat islets. In anaesthetized pigs, 15 min infusion of synthetic pig galanin (207 pmol min-1) into the pancreatic artery decreased the insulin output with a subsequent recovery. In vitro, pig galanin (10(-6) mol l-1) inhibited glucose- (8.3 mmol l-1) stimulated insulin release from isolated pig islets. We conclude that homologous galanin inhibits insulin secretion in both the rat and the pig.     

Platelet-rich plasma improves impaired glucose hemostasis,disrupted insulin secretion,and pancreatic oxidative stress in streptozotocin-induced diabetic rat

Abstract

Our study aimed to investigate the effects of platelet-rich plasma (PRP) on impaired glucose homeostasis, disrupted islet insulin secretion, and pancreatic oxidative status in streptozotocin (STZ)-diabetic rats. A total of 64 Sprague-Dawley male were randomized to four groups including controls, diabetes, control-PRP, and diabetes-PRP. The rats received the PRP (0.5?ml/kg, SC injection) twice weekly for 4 weeks. Plasma glucose and insulin levels, pancreatic oxidative stress markers and islet insulin secretion and content were measured. Compared with the control group, in the diabetic group, increased plasma glucose and malondialdehyde (MDA) levels and decreased plasma insulin level, islet insulin secretion, pancreatic superoxide dismutase (SOD), and catalase activities were observed. PRP treatment significantly reduced plasma glucose and MDA levels and enhanced plasma insulin, antioxidant enzyme activity, islet insulin secretion, and content in the diabetic rats. These findings showed that PRP can improve pancreatic islet insulin secretion, pancreatic oxidative stress and regulate plasma insulin and glucose levels in diabetic rats.     

甘丙肽抑制大鼠垂体腺瘤细胞体外侵袭性

目的 探讨甘丙肽对大鼠垂体腺瘤细胞侵袭性的作用及其受体机制.方法 提取大鼠垂体腺瘤GH3细胞RNA,反转录后测定甘丙肽及其3个受体亚型的表达情况;将大鼠垂体腺瘤GH3细胞分为对照组、甘丙肽药物处理组和选择性甘丙肽2型受体激动剂AR-M1896组,利用MTT方法检测对照组和实验组在给药后12、24和36 h各分组细胞活力...     

Enhancement of insulin secretion during selective blockade of α1, - and α2-adrenoceptors in the rat: Effects of somatostatin

The effects of somatostatin on plasma concentrations of insulin and glucose in the presence of the selective α₁-adrenoceptor blocking agent prazosin or the selective α₂-adrenoceptor blocking drug yohimbine were studied in vivo in anesthetized rats. Infusion of both prazosin (0.080 mg/min) and yohimbine (0.018 mg/min) increased plasma insulin levels within 10 min. Prazosin, but not yohimbine, caused a significant increment in plasma glucose concentration. Somatostatin (0.1 μg/min) promptly and extensively lowered plasma insulin concentrations during the infusion of both prazosin and yohimbine, suggesting that the inhibitory effect of somatostatin is not mediated via a direct action on α₁ or α₂-adrenoceptors. Plasma glucose concentration fell slightly during somatostatin administration. A marked increment in insulin release occurred in response to cessation of the somatostatin infusion, both during prazosin- and yohimbine-treatment. We conclude that somatostatin efficiently inhibits insulin secretion during selective α₁- and α₂-adrenoceptor blockade and, further, that the insulin off-response after somatostatin treatment is potentiated by α-adrenoceptor blockade. This study also indicates that blockade of α₁- as well as of α₂-adrenoceptors leads to an increased insulin secretion.     

Dynamics of insulin secretion in dogs with alloxan diabetes

Hypoinsulinemia in the superior pancreatico-duodenal vein and depression of the first phase of insulin secretion by the pancreas, characteristic of alloxan diabetes of different degrees of severity, are not observed in the femoral vein. The results of an investigation of the dynamics of the insulin and glucose concentrations in the superior pancreatico-duodenal vein emphasize the dominant role of the pancreatic factor in the pathogenesis of alloxan diabetes in dogs. Data obtained by the study of these indices in the peripheral femoral vein do not reflect this state of affairs adequately.Laboratory of Pathological Physiology, Institute of Experimental Endocrinology and Hormone Chemistry, Academy of Medical Sciences of the USSR, Moscow. Department of Normal Physiology, North-Ossetian Medical Institute, Ordzhonikidze. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Fedorov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 3, pp. 278–281. March, 1978.     

Effects of α- and β-adrenoceptor stimulation on 45Ca2+ efflux and insulin secretion from perfused rat islets

Exposure to the β₂-adrenoceptor agonist terbutaline resulted in a transient stimulation of ⁴⁵Ca²⁺ efflux from ⁴⁵Ca²⁺ preloaded rat islets perfused in 2 mm Ca²⁺ and 8.3 mm glucose. Concomitantly, an increase in insulin secretion occurred. Under the same experimental conditions, the α-adrenoceptor agonist noradrenaline promptly inhibited insulin release without any apparent influence on ⁴⁵Ca²⁺ efflux. In contrast, in a medium containing 2 mm Ca²⁺ and a low glucose concentration (2.8 mm), terbutaline stimulated insulin secretion without any apparent effects on ⁴⁵Ca²⁺ efflux. Noradrenaline had no effect on insulin secretion or ⁴⁵Ca²⁺ efflux in this medium. When islets were perfused with 8.3 mm glucose in a Ca²⁺ deficient medium, with or without addition of the chelating agent EGTA, terbutaline induced a marginal stimulation of insulin secretion and a negligible stimulation of ⁴⁵Ca²⁺ efflux. On the contrary, noradrenaline stimulated to an immediate and notable ⁴⁵Ca²⁺ efflux in these Ca²⁺ deficient media. Noradrenaline also clearly inhibited insulin secretion, though less markedly and with a slower onset than in islets perfused in 2 mm Ca²⁺. When the islets were perfused in a Ca²⁺ deficient medium with 2.8 mm glucose, terbutaline had a slight insulin releasing effect, but stimulated ⁴⁵Ca²⁺ efflux potently. Noradrenaline had no influence on insulin secretion but a weak stimulatory effect on ⁴⁵Ca²⁺ efflux. The data suggest that the β₂-adrenoceptor agonist terbutaline has the ability to stimulate insulin secretion in perfused rat islets, requiring extracellular Ca²⁺ for the full expression of its effects. These effects may be exerted through a Ca²⁺-Ca²⁺ exchange over the cell membrane and/or through cAMP and intracellular Ca²⁺ perturbations. Moreover, terbutaline directly stimulates ⁴⁵Ca²⁺ efflux, an effect inhibited by glucose. Further, the α-adrenoceptor agonist noradrenaline can inhibit insulin secretion in the absence of extracellular Ca²⁺, but the full expression of its inhibitory action is dependent on extracellular Ca²⁺ and glucose. In addition, noradrenaline stimulates ⁴⁵Ca²⁺ efflux in a Ca²⁺ deficient medium, an effect which appears independent of the glucose concentration.     

A role for islet peptide YY in the regulation of insulin secretion

The authors are grateful to Ms L. Bengtsson and Ms L. Kvist for technical assistance. The study was financially sup ported by The Swedish Medical Research Council (grants no. 14X-6834 and 12X-712); The Novo Nordic Founda tion; Swedish Diabetes Association; The Crafoord, Albert Pa~Olsson and Ernhold Lundstro~Dm Foundations and by the Faculty of Medicine, Lund University, Lund, Sweden.     

Myelin basic protein stimulates insulin and glucagon secretion from rat pancreatic islets in vitro and in vivo

The effect of myelin basic protein on insulin and glucagon secretion from rat pancreatic islets was studied in vivo and in vitro. The myelin basic proteins isolated from bovine, human and rat brains all stimulated insulin secretion in a similar fashion. In a static incubation of isolated pancreatic islets, myelin basic protein at doses of 15.6–250 μg in a 0.5-ml reaction volume (1.7 times 10^-8 to 2.7 times 10^-5 M) significantly stimulated hormone release. Maximal stimulation, obtained at the 250-μg dose, was 6.5-fold greater than control for insulin secretion and 6.7-fold greater than control for glucagon secretion. In the case of glucagon no saturation was observed, but saturation was obvious for insulin release at doses of myelin basic protein of 62.5–250μg, larger doses causing permeabilization of the islet membranes as indicated by leakage of acid phosphatase. At a 100-μg dose the time course of insulin secretion induced by myelin basic protein indicated a fast initial release, and after the first 2 h only a little more insulin was released. At the lower doses of myelin basic protein (11 and 33μg) the secretion rate was nearly constant after the first hour. Significant stimulation of glucagon release by myelin basic protein was seen after 60 min, the rate of release being roughly constant at 33-and 100-μg doses thereafter. At the 11-μg dose significant stimulation of hormone release was observed only after a 4-h incubation. Lowering the temperature from 37 to 27 and 20°C reduced both basal and stimulated hormone secretion, the extent of stimulation over the basal level remaining the same at all temperatures only for insulin secretion at a dose of myelin basic protein of 100 μg. A dose of 10 mg myelin basic protein injected intravenously into anaesthetized rats resulted 15 min after injection in a circulating concentration of myelin basic protein of 34.7 μg ml^-1 (1.7 times 10^-6 M) as measured by our radioimmunoassay. It stimulated insulin secretion (P < 0.01), having no significant effect on plasma glucagon levels. Since myelin basic proteins have been shown to display fusogenic properties in cell-free membrane systems, we propose that myelin basic protein exerts its hormone-releasing effect by aggregating and fusing the hormone-containing vesicles to the cell plasma membranes.     

Potentiation of glucose-induced insulin secretion in the perfused rat pancreas by porcine GIP (gastric inhibitory polypeptide), bovine GIP,and bovine GIP(139)

Porcine GIP (gastric inhibitory polypeptide) potentiates glucose-induced insulin secretion under a variety of experimental conditions. Recently GIP was isolated also from bovine intestine, and found to differ from porcine GIP by having isoleucine instead of lysine in position 37. We have compared the effects of porcine GIP to that of bovine GIP and bovine GIP_(]_₃₉₎ on glucose-induced insulin secretion from the perfused rat pancreas. We found that porcine GIP, bovine GIP, and bovine GIP_(l_₃₉₎ all strongly potentiated both first and second phases of glucose-induced insulin secretion (glucose concentration 6.7 mM; polypeptide concentration 1 nM). There was no significant difference between the polypeptides with regard to the potency to potentiate glucose-induced insulin secretion. We conclude that bovine GIP, as porcine GIP, potentiates glucose-induced insulin secretion, and that the insulinotropic activity of GIP is not confined to the last three amino acids at the C-terminal end.,     

Shock predictability and gastric secretion in the chronic gastric fistula rat

In Experiment 1 rats exposed to unpredictable grid shock demonstrated a significant decrease in gastric secretion and total acid output as compared to rats exposed to predictable shock and rats exposed only to the tone stimulus. In Experiment 2 rats were immobilized in restraint cages. Restraint plus predictable shock and restraint plus unpredictable shock resulted in a significant decrease in stomach acid output as compared to restrained no-shock controls. These results do not support a gastric hypersecretion hypothesis for studies which have reported the development of stomach ulcers by using unpredictable shock stress.     

Effects of impaired insulin secretion on the fertilization of mouse oocytes

We have studied the effect of moderately impaired maternal insulinsecretion on oocyte chromosomal constitution, fertilizationand zygote DNA synthesis. Female mice were injected with a singledose of streptozotocin (65 mg/kg) 14 days before fertilization/ovulation.Zygotes/oocytes were recovered from control and subdiabeticmice on day 1 of pregnancy. Compared with control animals, subdiabeticfemales showed a significant difference in the proportion ofzygotes/oocytes. The subdiabetic mothers had a lower percentageof zygotes and a higher percentage of unfertilized and degeneratedoocytes in comparison with control animals. The investigationof [³H]thymidine incorporation did not show any influence ofthe maternal subdiabetes on the initial zygote DNA synthesis.An analysis of the ovulated oocytes at the metaphase II stageisolated from subdiabetic mice did not reveal increased chromosomalanomalies in comparison with the controls. Control and subdiabeticmothers had a similar percentage of oocytes with a normal haploidset of chromosomes, and the incidence of aneuploidy/diploidydid not differ significantly. These observations suggest thatinsulin changes in subdiabetic mothers had a deleterious influenceon oocyte fertilization in mice, but apparently they did nothave any effect on the nuclear events.     

Contribution of galanin to stress-induced impairment of insulin secretion in swimming mice

This study examines the potential role of the neuropeptide, galanin, in stress-induced inhibition of insulin secretion in swimming mice. Firstly, the pancreatic and adrenal content of galanin-like immunoreactivity was determined in mice after swimming stress. It was found that pancreatic content was significantly lower in stressed mice than in resting controls, both after 2 (P < 0.05) and 6 (P < 0.025) minutes of swimming, suggesting partial release of pancreatic galanin during stress. In contrast, the adrenal content of galanin-like immunoreactivity did not change during the swimming stress. Gel filtration of tissue extracts indicated that (1) mouse pancreas contains two forms of galanin-like immunoreactivity; one co-eluting with synthetic porcine galanin (centred on K_av of 0.70) and another with a larger molecular weight (centred on K_av, of 0.30), and (2) mouse adrenal contains a small void volume-peak and a larger peak of immunoreactivity, the latter co-eluting with synthetic galanin. Secondly, the effects of swimming stress on plasma glucose and insulin levels were compared in mice that received high titre rabbit anti-galanin serum with those in mice receiving normal rabbit serum. In normal rabbit serum-pretreated swimming mice, glucose-induced insulin levels were only 50% of resting controls (P < 0.01). Immunoneutralization of galanin with specific antiserum abolished this swimming stress-induced inhibition of glucose-stimulated insulin levels. This was accompanied by a modestly enhanced rate of glucose disappearance. These findings suggest that pancreatic galanin is released during swimming stress in mice and that endogenous galanin makes a major contribution to stress-induced impairment of insulin secretion.     

Insulin sensitivity, insulin secretion, and metabolic and hormonal parameters in healthy women and women with polycystic ovarian syndrome

To study the contributions of body mass, body fat distribution and family history of type 2 diabetes mellitus to hyperinsulinaemia, insulin secretion and resistance in polycystic ovarian syndrome (PCOS), 17 lean (LC) and 17 obese (OC) healthy control subjects, and 15 lean (LPCOS) and 28 obese (OPCOS) women with PCOS were investigated. Waist:hip ratio (WHR), serum concentrations of sex steroids, glucose and insulin during a 75 g oral glucose tolerance test (OGTT), and insulin and C-peptide early phase secretion, and insulin sensitivity index using a euglycaemic hyperinsulinaemic clamp were assessed. The PCOS subjects had a higher mean WHR than the controls. A trend towards hyperinsulinaemia and impairment of insulin sensitivity (including the rates of both glucose oxidation and non-oxidation) was observed in LPCOS subjects, but only in OPCOS subjects were these changes significant. Early phase insulin secretion but not the early phase C-peptide secretion was increased in PCOS subjects compared to controls, suggesting that peripheral hyperinsulinaemia in PCOS women was mainly due to the observed lowered hepatic insulin extraction and insulin resistance in skeletal muscle. Moreover, the presence of a family history of type 2 diabetes did not affect early phase insulin or C-peptide secretion in the PCOS group. These results confirm and strengthen earlier contentions, that insulin resistance is a characteristic defect in PCOS and is worsened particularly by abdominal obesity.     

Subcellular B cell calcium and insulin secretion in vitro

Summary Using the ultracytochemical pyroantimonate technique different patterns of calcium containing precipitates were found in the B cells of the isolated perfused rat pancreas under conditions of stimulated and inhibited insulin secretion. The calcium specificity of the ultracytochemical method was assessed by perfusion with a EGTA containing calcium-free medium, which markedly reduced the extent of precipitation. Perfusion with 20 mM D-glucose over a period of 30 min resulted in calcium distribution patterns which could be related to the biphasic insulin release. The calcium patterns differed significantly in their quality and quantitative morphometry from those after 5 mM D-glucose or cyproheptadine (CPH) perfusion (20 mM D-glucose plus 0.1 mM CPH). After 3–5 min of 20 mM glucose perfusion there was an increased calcium precipitation along the inner side of the B cell membranes. After 20–30 min an additional increase in precipitation was found in the cytoplasmic matrix and in the secretory granules. B cells in a CPH-inhibited state of secretion and also after perfusion with 5 mM glucose lacked these findings. The data suggest that an increase in the membrane associated calcium may induce the first phase of insulin secretion by triggering the exocytosis of peripheral granules, while the cytoplasmic calcium may be involved in long term regulation of insulin release.Supported by Deutsche Forschungsgemeinschaft, KL 366/1     

Reflex insulin secretion due to central hyperglycemia promoted by intracarotid glucose infusion in dogs

The reflex insulin secretion was investigated by glucose infusions (10 ml of 3% solutions) into the carotid artery or the jugular vein in anesthetized and unanesthetized, untrained dogs. Neither intrajugular nor intracarotideal glucose infusions changed the peripheral glycemic level in any of the experiments. Reflex insulin secretion did occur when glucose was injected into the carotid artery under pentobarbital anesthesia (30 mg/kg IV), but not in unanesthetized animals. Saline infusion into the carotid artery or glucose into the jugular vein in both groups did not elicit a significant increase in insulin secretion.     

Antipyretic Effect of Neuropeptide Galanin in Endotoxin-Induced Fever

Neuropeptide galanin produces a antipyretic effect in experimental pyrogenic reaction induced by intraperitoneal injection of lipopolysaccharide. Central intracerebroventricular injection of 100 ng galanin significantly attenuated, but did not completely abolish fever. Central galanin injection potentiated endotoxin-induced activation of the noradrenergic system and blocked activation of the serotoninergic system of the anterior hypothalamus.     

Association of a type 2 diabetes genetic risk score with insulin secretion modulated by insulin sensitivity among Chinese Hans

Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion. The present study aimed to identify the influence of insulin sensitivity on the genetic risk of impaired insulin secretion among a Chinese Han population. For 3229 controls and 1994 treatment‐naïve T2D, single nucleotide polymorphisms (SNPs) from 24 T2D‐related genomic loci were genotyped and a genetic risk score (GRS) was constructed. Results showed that GRS was associated with insulin secretion and disposition indices in both controls and treatment‐naïve T2Ds. Upon stratifying the participants into tertiles by the Matsuda index, we observed an inhibitory relationship between the GRS and insulin secretion in low insulin sensitive but not in high insulin sensitive controls and treatment‐naïve T2Ds. Moreover, low insulin sensitive individuals exhibited more severe impairment in insulin secretion and beta cell response to insulin sensitivity with an increase in risk alleles. Our findings identified that the association of GRS with insulin secretion was strongly modulated by insulin sensitivity in both controls and T2Ds of Chinese Han. It indicates that insulin sensitization should be emphasized in prevention and treatment of T2D for beta cell protection.     

Ca++-dependent serotonin secretion from the rat hypothalamus during ontogeny

Laboratory of Hormonal Regulation, N. K. Kol'tsov Institute of Developmental Biology, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Orekhovich.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 8, pp. 166–169, August, 1989.