Mechanisms involved in the depleting effect of cysteamine on pancreatic somatostatin

We investigated the effects of cysteamine on the pancreatic islet hormones and found that pancreatic somatostatin contents depleted 60 min after the oral administration of cysteamine (300 mg/kg) to rats, yet the insulin and glucagon contents remained unchanged. When pancreatic islets isolated by collagenase digestion were incubated for 60 min in Krebs-Ringer bicarbonate buffer containing 0.1, 1, or 10 mM cysteamine, cysteamine dose-dependently decreased the somatostatin content, however, only a high concentration (10 mM) decreased the insulin level, and cysteamine exerted no effect on the glucagon content. The islet hormones (synthetic somatostatin-14, synthetic somatostatin-28, extracted pork insulin and extracted pork glucagon) were incubated for 60 min with cysteamine (0.1, 1, or 10 mM) and somatostatin-14 was found to be markedly decreased by 1 mM cysteamine. Pork insulin but not pork glucagon was dose-dependently decreased by 0.1-10 mM cysteamine. Cysteamine, 0.1-1 mM, did not interfere with the radio-immunoassay system for somatostatin or insulin, although 10 mM cysteamine did so. This compound exerted no effect on the radioimmunoassay system for glucagon. Our studies support earlier findings that cysteamine administered to experimental animals plays a role of relatively specific depletor of somatostatin. The possibility that the depletion of somatostatin is in part due to the remarkable sensitivity of the intracellular compartments of the D cells to the drug and in part due to the remarkable sensitivity of the molecular structure of somatostatin has to be considered.     

Effect of Local Injection of Cysteamine and Cystamine on Somatostatin and Neuropeptide Y Levels in the Rat Striatum

Cysteamine and its dimeric form cystamine have been applied to the rat striatum by local injection. Both compounds resulted in a dose-dependent decrease of somatostatin levels. Maximal reduction of somatostatin (by about 50%) was obtained at a dose of 50 micrograms of cysteamine or cystamine after about 6 h. All three molecular weight forms of somatostatin--somatostatin-14, somatostatin-28, and the 13,000 molecular weight form of somatostatin--were reduced, as shown by size exclusion HPLC. Injection of radiolabeled cystamine revealed a fast conversion of the compound to cysteamine, suggesting it is active in the monomeric form. The levels of neuropeptide Y, which is colocalized with somatostatin in striatal neurons, failed to be changed by local or intraperitoneal injection of cysteamine, suggesting that this treatment does not affect vesicles of somatostatin/neuropeptide Y neurons.     

Pancreatic and gut hormones during fasting: insulin, glucagon, and somatostatin

When adult male rats were fasted for 24 or 72 h there was no change in the pancreatic content of insulin or glucagon, but the somatostatin content increased at 72 h. This contrasts with earlier reports of reduced pancreatic somatostatin after fasting. After a 48-hour fast there was an increase in the concentration of duodenal somatostatin, and a tendency toward reduced concentrations in stomach, jejunum, and ileum. When duodenal mucosa and muscle extracts were chromatographed the relative amounts of putative somatostatin-28 and somatostatin-14 were unchanged. Insulin secretion from the perfused pancreata of 72-hour-fasted rats was markedly reduced, but glucagon and somatostatin secretion was indistinguishable from that of fed controls. These results indicate that in spite of the marked alterations of nutrient metabolism and insulin secretion which occur during fasting, the pancreatic content of insulin, glucagon and somatostatin and the gut concentration of somatostatin are well maintained.     

Neuro-endocrine basis for altered plasma glucose homeostasis in the Fragile X mouse

Background

The fragile X mouse model shows an increase in seizure susceptibility, indicating an involvement of the GABAergic system via an alteration in cellular excitability. In the brain, we have previously described a reduction in GABA_A receptor expression as a likely basis for this susceptibility. In the brains of fragile X mice, this reduction in receptor expression culminates with a concomitant increase in the expression of glutamic acid decarboxylase (GAD), the enzyme responsible for GABA synthesis. Further, voltage-sensitive calcium channel expression is reduced in the pancreas of the fragile X mouse. Since there are considerable similarities in the GABAergic system in the brain and pancreas, we evaluated the protective role of taurine in pancreatic islet development in both wild type (WT) and fragile X mice (KO).

Methods

One-month-old FVB/NJ males or age-matched fmr1-knockout (KO) mice were supplemented with taurine in drinking water (0.05% w/v) for four weeks. Age-matched controls were fed water only for the same duration. At four weeks, mice were sacrificed and pancreases processed for histology and immunohistochemical studies on changes of insulin, glucagon and somatostatin expression. Additional mice were subjected to a glucose tolerance test.

Results

Taurine treatment resulted in a significant increase in the number and size of islets. WT taurine-fed mice, slightly hypoglycemic prior to glucose injection, showed significantly reduced plasma glucose at 30 min post-injection when compared to control mice. KO mice had normal baseline plasma glucose concentration; however, following glucose injection they had higher plasma glucose levels at 30 min when compared to controls. Supplementation of taurine to KO mice resulted in reduced baseline levels of plasma glucose. After glucose injection, the taurine-fed KO mice had reduced plasma glucose at 30 min compared to KO. Concomitant with the increased islets size and glucose tolerance observed in taurine-fed mice there was an increase in insulin, glucagon and somatostatin immunoreactivity in the islets of WT mice. In the KO mice however, insulin levels were not affected whereas glucagon and somatostatin levels were reduced. Exocytosis of these hormones is calcium-dependent, therefore any exacerbation of calcium homeostasis could affect hormone release. We found the expression of the voltage sensitive calcium channels (VSCC) is drastically reduced in the pancreas of fragile X mice.

Conclusions

During early development, the VSCC play an important role in calcium-dependent gene expression. Since these channels are also involved in depolarization and calcium-mediated vesicular release of neurotransmitters and pancreatic hormones, alterations in the expression of VSCC not only will affect calcium-mediated gene expression but also hormonal and neurotransmitter release creating therefore a neuroendocrine perturbation in the fragile X that may potentially affect other organ systems. We find that in the fragile X mouse, taurine treatment may partially restore functionality of the neuro-endocrine pancreas.

     

Effects of cysteamine administration on plasma concentration of metabolites, pancreatic glucagon and insulin in the chicken

1. The effects of subcutaneous injection of cysteamine (2-mercaptoethylamine, 300 mg/kg) were investigated in 5-6 week-old chickens. 2. In the short term (1 hr), cysteamine increased plasma levels of glucose, free fatty acids and insulin, and decreased that of alpha-amino non protein nitrogen. 3. In a longer term (17-24 hr), cysteamine increased the plasma level of glucose, did not modify those of alpha-amino non protein nitrogen, insulin and glucagon and decreased that of free fatty acids. 4. The disposal of an oral glucose load was impaired and the glucose-induced inhibition of pancreatic glucagon and stimulation of insulin release were blunted 17 hr after cysteamine administration. 5. Therefore, cysteamine exerts multiple effects on chicken pancreatic islet cells.     

Effects of cysteamine on pro-somatostatin related peptides

Intracerebroventricular (icv) injection of cysteamine to rats produced a marked depletion of somatostatin-14-like immunoreactivity (LI) in all rat brain regions examined. The somatostatin-28 (SS28)-LI and SS28(1-12)-LI were generally not altered by the cysteamine treatment. Following subcutaneous injection of the drug similar depletions of hypothalamic SS14-LI was observed with no change in SS28-LI nor SS28(1-12)-LI. In vitro cysteamine significantly increased the basal release of SS14-LI and markedly potentiated the evoked release of SS14-LI from hypothalamic slices. At 10 mM cysteamine, enhanced release of SS14-LI from hypothalamic slices was still observed despite a marked depletion of tissue content of SS14-LI.     

Cysteamine exerts multiple effects on the endocrine cells of the rat pancreas

We have studied the effects by cysteamine in vitro and in vivo on hormone production and islet cell metabolism in isolated pancreatic islets and perfused pancreas of the rat. In isolated islets, cysteamine dose-dependently depleted somatostatin immunoreactivity by 50% after 60 min exposure to 1 mmol/l of the compound. This effect appeared to be independent of interaction of the drug with secretion of somatostatin from the pancreatic D-cells. Cysteamine, however, interacted acutely not only with the D-cells, but also markedly suppressed glucose-induced insulin release. Moreover, cysteamine inhibited islet glucose oxidation, an effect which reflects interference with the metabolism mainly of the B-cells. The effect of cysteamine on glucose-induced insulin release was prolonged, since it was still observed in the isolated rat pancreas perfused 24 h after in vivo treatment with cysteamine. In contrast to the effects on glucose-induced insulin release, the response to glibenclamide remained unaffected by a previous exposure to cysteamine in vivo. However, both glucose- and glibenclamide-induced somatostatin secretion was reduced by 50%, whereas basal glucagon secretion was significantly enhanced in pancreata from cysteamine-treated rats vs. control rats. We conclude that (1) cysteamine does not specifically affect the D-cells of the islets, and (2) the multiple effects by cysteamine on islet cell function, particularly on B-cell metabolism and secretion, renders the compound unsuitable for the study of paracrine interactions in the islets.     

Light and electron microscopical immunocytochemical localization of pancreastatin-like immunoreactivity in porcine tissues

Summary Pancreastatin is a 49 amino acid comprising peptide isolated from porcine pancreas that is derived by proteolytic processing from chromogranin A. Using an antibody against the synthetic C-terminal fragment pancreastatin (33–49), we examined the light and electron microscopical immunocytochemical localization of this peptide in porcine tissues. Pancreastatin-like immunoreactivity (PLI) was found in pancreatic somatostatin-, insulin- and glucagon cells in varying intensities; pancreatic polypeptide cells were always negative. At the electron microscopical (EM) level the immunoreactivity was confined to the electron dense core of the secretory granules in the case of somatostatin and insulin cells or to the less electron dense halo of the glucagon granules. In the antrum PLI positive cells represented gastrin (G), somatostatin (D) and enterochromaffin (EC) cells, in the duodenum in addition to EC- and G-cells a small number of PLI positive cells showed a positive immunoreaction for glucagon-like peptide (GLP) I and secretin in serial sections. Both norepinephrine and epinephrine containing cells of the adrenal medulla exhibited a strong reaction for PLI. In the pituitary several cell populations stained with varying intensities, including gonadotrophs and thyrotrophs. PLI is present in a distinct and characteristic subpopulation of neuroendocrine cells in various organs. The subcellular localization may indicate a function in the granular concentration, packaging and storage of peptides and amines in the brain-gut endocrine system.     

Inhibitory effect of somatostatin-28 on pancreatic polypeptide, glucagon and insulin secretion in normal man

We have compared the effects of equimolar doses of intravenous somatostatin-28 (SS-28) and somatostatin-14 (SS-14) (250 micrograms and 125 micrograms, respectively) on the secretion of pancreatic polypeptide (PP), glucagon and insulin evoked by a protein-rich meal in normal subjects. Both peptides reduced the fasting plasma levels of these hormones and completely abolished their responses to the alimentary stimulus; in addition, they caused an early decrease of plasma glucose followed by a hyperglycemic phase. As compared to SS-14, SS-28 elicited a longer-lasting inhibition of PP and insulin secretion and displayed greater hypo- and hyperglycemic effects. A somatostatin-like component, similar to SS-28, has been identified in pancreatic extracts as well as in peripheral plasma. Thus, it might be hypothesized that this peptide plays a role in the control of pancreatic hormone release.     

Multiple subcutaneous injections of somatostatin induce tachyphylaxis of the suppression of plasma insulin, but not glucagon, in the rat

The time course of pancreatic effects of somatostatin was studied over a period of 2 h in unanesthetized unrestrained rats after administration of the peptide by intravenous infusion and by single and multiple subcutaneous injections. During infusion of 10 and 30 micrograms/kg per min, somatostatin continuously suppressed plasma insulin and plasma glucagon. Plasma glucose was significantly increased at the lower dose, but not affected at the higher dose. Single subcutaneous injections of 0.3 and 3 mg/kg decreased plasma insulin and glucagon dose-dependently for 20-60 min without affecting plasma glucose. Multiple subcutaneous injections of somatostatin (one to four doses of 3 mg/kg, administered at intervals of 30 min) caused an initial decrease of plasma insulin (at 30 min), a rebound-increase at 60 and 90 min, and a final return to control values by 120 min. Plasma glucagon remained continuously suppressed. Plasma glucose increased significantly at 60 and 90 min and tended to return towards control values thereafter. In conclusion, pancreatic B cells - but not A cells - of the rat develop tachyphylaxis to somatostatin within 2 h after multiple subcutaneous injections of the peptide. By this mode of administration, 'selective' suppression of plasma glucagon can be achieved with somatostatin in the rat.     

Somatostatin, insulin and glucagon secretion by the perfused pancreas from the cysteamine-treated rat

In rats, administration of a single dose of cysteamine (300 mg/kg, intragastrically) induces a depletion of pancreatic somatostatin content (approximately 60%) without modifying pancreatic insulin or glucagon content. In perfused pancreases from cysteamine-treated rats, there was a lack of somatostatin response to glucose, arginine or tolbutamide. In the absence of stimulated somatostatin release, the secretory responses of insulin and glucagon to glucose, to arginine, and to tolbutamide were not significantly different from those observed in pancreases from control rats. Our data do not support the concept that pancreatic somatostatin plays a major role in the control of insulin and glucagon release.     

The effect of hypophysectomy on pancreatic islet hormone and insulin-like growth factor I content and mRNA expression in rat

The growth arrest after hypophysectomy in rats is mainly due to growth hormone (GH) deficiency because replacement of GH or insulin-like growth factor (IGF) I, the mediator of GH action, leads to resumption of growth despite the lack of other pituitary hormones. Hypophysectomized (hypox) rats have, therefore, often been used to study metabolic consequences of GH deficiency and its effects on tissues concerned with growth. The present study was undertaken to assess the effects of hypophysectomy on the serum and pancreatic levels of the three major islet hormones insulin, glucagon, and somatostatin, as well as on IGF-I. Immunohistochemistry (IHC), in situ hybridization (ISH), radioimmunoassays (RIA), and Northern blot analysis were used to localize and quantify the hormones in the pancreas at the peptide and mRNA levels. IHC showed slightly decreased insulin levels in the cells of hypox compared with normal, age-matched rats whereas glucagon in cells and somatostatin in cells showed increase. IGF-I, which localized to cells, showed decrease. ISH detected a slightly higher expression of insulin mRNA and markedly stronger signals for glucagon and somatostatin mRNA in the islets of hypox rats. Serum glucose concentrations did not differ between the two groups although serum insulin and C-peptide were lower and serum glucagon was higher in the hypox animals. These changes were accompanied by a more than tenfold drop in serum IGF-I. The pancreatic insulin content per gram of tissue was not significantly different in hypox and normal rats. Pancreatic glucagon and somatostatin per gram of tissue were higher in the hypox animals. The pancreatic IGF-I content of hypox rats was significantly reduced. Northern blot analysis gave a 2.6-, 4.5-, and 2.2-fold increase in pancreatic insulin, glucagon, and somatostatin mRNA levels, respectively, in hypox rats, and a 2.3-fold decrease in IGF-I mRNA levels. Our results show that the fall of serum IGF-I after hypophysectomy is accompanied by a decrease in pancreatic IGF-I peptide and mRNA but by partly discordant changes in the serum concentrations of insulin and glucagon and the islet peptide and/or mRNA content of the three major islet hormones. It appears that GH deficiency resulting in a low IGF-I state affects translational efficiency of these hormones as well as their secretory responses. The maintenance of normoglycemia in the presence of reduced insulin and elevated glucagon serum levels, both of which would be expected to raise blood glucose, may result mainly from the enhanced insulin sensitivity, possibly due to GH deficiency and the subsequent decrease in IGF-I production.     

Stimulatory effect of xenin-8 on insulin and glucagon secretion in the perfused rat pancreas

Xenin is a 25-amino acid peptide of the neurotensin/xenopsin family identified in gastric mucosa as well as in a number of tissues, including the pancreas of various mammals. In healthy subjects, plasma xenin immunoreactivity increases after meals. Infusion of the synthetic peptide in dogs evokes a rise in plasma insulin and glucagon levels and stimulates exocrine pancreatic secretion. The latter effect has also been demonstrated for xenin-8, the C-terminal octapeptide of xenin. We have investigated the effect of xenin-8 on insulin, glucagon and somatostatin secretion in the perfused rat pancreas. Xenin-8 stimulated basal insulin secretion and potentiated the insulin response to glucose in a dose-dependent manner (EC(50)=0.16 nM; R(2)=0.9955). Arginine-induced insulin release was also augmented by xenin-8 (by 40%; p<0.05). Xenin-8 potentiated the glucagon responses to both arginine (by 60%; p<0.05) and carbachol (by 50%; p<0.05) and counteracted the inhibition of glucagon release induced by increasing the glucose concentration. No effect of xenin-8 on somatostatin output was observed. Our observations indicate that the reported increases in plasma insulin and glucagon levels induced by xenin represent a direct influence of this peptide on the pancreatic B and A cells.     

饥饿对大鼠胰岛素分泌的影响及其机制的分析

本工作探讨了大鼠饥饿时胰岛素分泌减少的机制。大鼠连续饥饿1至4d,其血浆胰岛素水平的变化不与血糖平行,二者虽均于饥饿第1天即显著下降,但胰岛素在饥饿期间一直维持于低水平。而血糖则于饥饿第3天开始回升,第4天接近正常水平。在离体实验中发现,禁食3d大鼠的离体灌流胰腺对精氨酸的胰岛素分泌反应明显地低于正常摄食大鼠。看来,饥饿时胰岛素分泌的减少似不是由于营养物质对胰岛β细胞刺激作用的减弱,而可能是由于局部抑制性影响加强所致。 我们进一步观察了胰内生长抑素的作用,发现饥饿3d的大鼠,在胰岛素分泌减少的同时,胰腺生长抑素的含量增高,如预先给动物注射半胱胺以耗竭内源性生长抑素,则使饥饿大鼠胰岛素分泌的抑制现象明显减轻。在离体实验中也发现,预先注射半胱胺的饥饿大鼠,其离体灌流的胰腺对精氨酸的反应恢复正常。这些结果提示,胰内生长抑素对β细胞局部抑制作用的增强,可能是饥饿引起胰岛素分泌减少的机制之一。     

Ultrastructural distribution of somatostatin-14 and-28 in rat adrenal cells

Summary Previous studies have shown that somatostatin modulates angiotensin-induced aldosterone secretion by adrenal glomerulosa cells. This effect is mediated through specific receptors which do not show any preference for somatostatin-14 (S14) or the N-extended form somatostatin-28 (S28). The study of the distribution of ¹²⁵I-Tyr [Tyr⁰, DTrp⁸] S14-and ¹²⁵I-Tyr[Leu⁸, DTrp²², Tyr²⁵] S28-binding in frozen sections of the rat adrenal by autoradiography indicated that both peptides bind to similar loci. High concentrations of binding sites were observed in the zona glomerulosa, and low concentrations were detected in the medulla. At the ultrastructural level, immunocytochemistry after cryoultramicrotomy revealed endogenous S14-and S28-like immunoreactive material in zona glomerulosa and in medulla. In glomerulosa cells, immunoreactive material was localized at the plasma membrane level, in the cytoplasmic matrix, in the mitochondria, and in the nucleus. S14-and S28-like materials were detected in both epinephrine and norepinephrine-storing cells of the adrenal medulla. In these cells, the distribution of either immunoreactive product was similar; it was observed in cytoplasmic matrix, secretory granules and nucleus, but not at the plasma membrane level. In situ hybridization does not reveal somatostatin mRNA in zona glomerulosa or medulla. These results demonstrate that S14 and S28 bind to, and are taken up by zona glomerulosa and adrenal medullary cells, but are not produced by these cells.     

Glucose,insulin and renin activity after sodium loading and depletion in Vipera aspis

Sodium, potassium, chloride, glucose, insulin and renin activity were investigated in fasted Vipera aspis subjected for 3 days to administration of 3% NaCl 5 ml, or injection of a diuretic and water loading to produce sodium depletion. After sodium loading, plasma sodium and glucose were significantly elevated if compared with those of controls, while plasma renin-like activity and plasma insulin were depressed. The insulin and somatostatin producing cells (B- and D-cells) showed only a weak immunoreactivity, while in the glucagon producing cells (A-cells) the immunoreactivity was stronger if compared with the handled controls. After sodium depletion, plasma sodium and glucose were significantly depressed and plasma renin-like activity and plasma insulin were significantly elevated. A strong immunoreactivity was present in B- and D-cells and only a weak immunoreactivity was detectable in the A-cells. These data suggest that the secretory activity of the endocrine pancreas and kidney may be affected, in vipers, by sodium and/or volume status.     

Biological actions of peptide YY: effects on endocrine pancreas, pituitary-adrenal axis, and plasma catecholamine concentrations in the dog

The present study was designed to gather information on the biological activity of peptide YY (PYY) in conscious dogs. PYY was infused intravenously at a dose of 238 pmol/kg X h, and plasma concentrations of glucose, insulin, pancreatic polypeptide (PP), ACTH, cortisol and catecholamines (norepinephrine-NE; epinephrine-E; dopamine-DA) were subsequently measured. PYY significantly increased plasma insulin levels transiently without effect on plasma glucose, but decreased plasma PP levels during all infusion periods. PYY stimulated both plasma ACTH and cortisol secretion, and this action of PYY was also shared by PP, with PP being less potent in ACTH-cortisol release. PYY further elicited specific changes in plasma catecholamine concentrations, i.e. an increase of NE but not of E, which were in contrast to the effects of insulin-induced hypoglycemia. PP failed to alter plasma insulin and catecholamine concentrations. These results suggest that PYY can affect anterior pituitary hormone secretion, sympathetic nervous outflow and pancreatic endocrine activity in addition to its known actions on gastric and pancreatic secretion in the dog.     

Central effects of DN1417, a novel TRH analog, on plasma glucose and catecholamines in conscious rats

Intracerebroventricular (icv) injection of DN1417 (0.3, 3 and 30 nmol/rat), a TRH analog, resulted in a dose-related increase in plasma glucose, epinephrine and norepinephrine levels in conscious male rats. The effects of DN1417 were more potent and longer-lasting than those of TRH on a molar basis. Intravenous injection of DN1417 (30 nmol/rat) did not change plasma glucose, epinephrine and norepinephrine levels. Pretreatment with hexamethonium (1.5 mg/100 g body wt, iv, 2 min before) inhibited plasma glucose, epinephrine and norepinephrine responses to DN1417 (3 nmol/rat, icv). DN1417 did not change plasma glucose, epinephrine and norepinephrine levels in rats after total adrenalectomy. In the animals pretreated with cysteamine (30 mg/100 g body wt, sc, 4 h before), basal plasma glucose, epinephrine and norepinephrine levels were raised, and exaggerated responses of plasma glucose, epinephrine and norepinephrine to DN1417 (3 nmol/rat, icv) were obtained. These results indicate that DN1417 has a potent and long-lasting effect in the central nervous system in stimulating the secretion of catecholamines through the autonomic nervous system, which is associated with an elevation of plasma glucose and that endogenous hypothalamic somatostatin may inhibit the action of DN1417.     

Phe-met-arg-phe-amide (FMRF-NH2) inhibits insulin and somatostatin secretion and anti-FMRF-NH2 sera detects pancreatic polypeptide cells in the rat islet

FMRF-NH2-like immunoreactivity was localized in the pancreatic polypeptide containing cells of the rat islet. FMRF-NH2 was investigated with regard to its effect on insulin, somatostatin and glucagon secretion from the isolated perfused rat pancreas. FMRF-NH2 (1 microM) significantly inhibited glucose stimulated (300 mg/dl) insulin release (p less than 0.005) and somatostatin release (p less than 0.01) from the isolated perfused pancreas. FMRF-NH2 (1 and 10 microM) was without effect on glucagon secretion, either in low glucose (50 mg/dl), high glucose (300 mg/dl), or during arginine stimulation (5 mM). These findings indicate that these FMRF-NH2 antisera recognize a substance in the pancreatic polypeptide cells of the islet which may be capable of modulating islet beta and D cell activity.     

Taurine regulates insulin release from pancreatic beta cell lines

Background

Pancreatic β-cells release insulin via an electrogenic response triggered by an increase in plasma glucose concentrations. The critical plasma glucose concentration has been determined to be ~3 mM, at which time both insulin and GABA are released from pancreatic β-cells. Taurine, a β-sulfonic acid, may be transported into cells to balance osmotic pressure. The taurine transporter (TauT) has been described in pancreatic tissue, but the function of taurine in insulin release has not been established. Uptake of taurine by pancreatic β-cells may alter membrane potential and have an effect on ion currents. If taurine uptake does alter β-cell current, it might have an effect on exocytosis of cytoplasmic vesicle. We wished to test the effect of taurine on regulating release of insulin from the pancreatic β-cell.

Methods

Pancreatic β-cell lines Hit-TI5 (Syrian hamster) and Rin-m (rat insulinoma) were used in these studies. Cells were grown to an 80% confluence on uncoated cover glass in RPMI media containing 10% fetal horse serum. The cells were then adapted to a serum-free, glucose free environment for 24 hours. At that time, the cells were treated with either 1 mM glucose, 1 mM taurine, 1 mM glucose + 1 mM taurine, 3 mM glucose, or 3 mM glucose + 1 mM taurine. The cells were examined by confocal microscopy for cytoplasmic levels of insulin.

Results

In both cell lines, 1 mM glucose had no effect on insulin levels and served as a control. Cells starved of glucose had a significant reduction (p<0.001) in the level of insulin, but this level was significantly higher than all other treatments. As expected, the 3 mM glucose treatment resulted in a statistically lower (p<0.001) insulin level than control cells. Interestingly, 1 mM taurine also resulted in a statistically lower level of insulin (p<0.001) compared to controls when either no glucose or 1 mM glucose was present. Cells treated with 1 mM taurine plus 3 mM glucose showed a level of insulin similar to that of 3 mM glucose alone.

Conclusions

Taurine administration can alter the electrogenic response in β-cell lines, leading to a change in calcium homeostasis and a subsequent decrease in intracellular insulin levels. The consequence of these actions could represent a method of increasing plasma insulin levels leading to a decrease in plasma glucose levels.