scholarly journals Studies With the Autotransplanted Ovine Pancreas: Glucagon and Insulin Secretion

1976 ◽  
Vol 29 (3) ◽  
pp. 223 ◽  
Author(s):  
AC Arcus ◽  
M Jane Ellis ◽  
RD Kirk ◽  
DW Beaven ◽  
RA Donald ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Direct Effect ◽  
Sodium Butyrate ◽  
Glucagon Secretion ◽  
Exocrine Secretion ◽  
Insulin Administration ◽  
Basic Studies ◽  
Glucagon And Insulin

Basic studies on the secretion of glucagon and insulin by the ovine pancreatic autotransplant in the neck are described. Of the 17 transplants in the series none failed to secrete glucagon and only three failed to secrete insulin in detectable amounts. The longest surviving transplant actively secreted both hormones 3 years after transplantation and five other transplants were functional and the animals healthy after 16 months. Exocrine secretion disappears shortly after transplantation. Sodium butyrate and alanine each promoted the secretion of both hormones by the transplant. Glucagon failed to promote insulin secretion by the transplant, although it apparently stimulated the ovine in situ pancreas. The immediate (presumably direct) effect of insulin was to inhibit transplant glucagon secretion. Hypoglycaemia induced by peripheral insulin administration failed to stimulate glucagon secretion by the transplant, although it did promote glucagon secretion by the ovine in situ pancreas. Heparin did not markedly suppress basal transplant secretion of either glucagon or insulin.

Evidence of a paracrine role for pancreatic somatostatin in vivo

1983 ◽  
Vol 245 (6) ◽  
pp. E598-E603 ◽  
Author(s):  
G. J. Taborsky
Keyword(s):  
Insulin Release ◽  
Glucagon Secretion ◽  
Base Line ◽  
Anesthetized Dogs ◽  
D Cells ◽  
Glucagon And Insulin ◽  
Line P ◽  
A And B Cells

Somatostatin (SS) in the D cells of the pancreatic islets has been hypothesized to tonically inhibit the secretion of glucagon and insulin from the neighboring A and B cells. To test this hypothesis directly, a nonimmunoreactive analogue of somatostatin [( D-Ala5-D-Trp8]SS) was infused intravenously at 0.55–17 micrograms/min into anesthetized dogs to suppress the secretion of pancreatic somatostatin and observe the effects of that suppression on glucagon and insulin release. Infusions of this analogue into anesthetized dogs at both a low dose (1.7 micrograms X min-1 X 30 min iv, n = 7) and at a medium dose (5.5 micrograms X min-1 X 30 min iv, n = 7) suppressed the release of somatostatin-like immunoreactivity (SLI) from the in situ canine pancreas by 31 +/- 10% of base line (P less than 0.025) and 45 +/- 6% of base line (P less than 0.0005), respectively. These doses increased glucagon secretion markedly (by 179 +/- 39 and 250 +/- 60% of base line, both P less than 0.005) and increased insulin secretion moderately (by 35 +/- 17 and 62 +/- 27% of base line, respectively, both P less than 0.05). The highest dose of analogue (17 micrograms/min, n = 9) produced less stimulation of glucagon release (delta = +95 +/- 35% of basal, P less than 0.025) and marked inhibition of insulin release (delta = -61 +/- 9% of basal, P less than 0.0005) despite a larger inhibition of pancreatic SLI release (delta = -84 +/- 3% of basal, P less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Glucagonotropic and Glucagonostatic Effects of KATP Channel Closure and Potassium Depolarization

Endocrinology ◽  
2020 ◽  
Vol 162 (1) ◽  
Author(s):  
Eike Früh ◽  
Christin Elgert ◽  
Frank Eggert ◽  
Stephan Scherneck ◽  
Ingo Rustenbeck
Keyword(s):  
Insulin Secretion ◽  
Beta Cells ◽  
Katp Channel ◽  
Glucagon Secretion ◽  
Alpha Cells ◽  
High Potassium ◽  
Intrinsic Signal ◽  
Mouse Islets ◽  
Glucagon And Insulin

Abstract The role of depolarization in the inverse glucose-dependence of glucagon secretion was investigated by comparing the effects of KATP channel block and of high potassium. The secretion of glucagon and insulin by perifused mouse islets was simultaneously measured. Lowering glucose raised glucagon secretion before it decreased insulin secretion, suggesting an alpha cell–intrinsic signal recognition. Raising glucose affected glucagon and insulin secretion at the same time. However, depolarization by tolbutamide, gliclazide, or 15 mM KCl increased insulin secretion before the glucagon secretion receded. In contrast to the robust depolarizing effect of arginine and KCl (15 and 40 mM) on single alpha cells, tolbutamide was of variable efficacy. Only when applied before other depolarizing agents had tolbutamide a consistent depolarizing effect and regularly increased the cytosolic Ca2+ concentration. When tested on inside-out patches tolbutamide was as effective on alpha cells as on beta cells. In the presence of 1 µM clonidine, to separate insulinotropic from glucagonotropic effects, both 500 µM tolbutamide and 30 µM gliclazide increased glucagon secretion significantly, but transiently. The additional presence of 15 or 40 mM KCl in contrast led to a marked and lasting increase of the glucagon secretion. The glucagon secretion by SUR1 knockout islets was not increased by tolbutamide, whereas 40 mM KCl was of unchanged efficiency. In conclusion a strong and sustained depolarization is compatible with a marked and lasting glucagon secretion. KATP channel closure in alpha cells is less readily achieved than in beta cells, which may explain the moderate and transient glucagonotropic effect.

Adrenergic modulation of pancreatic glucagon and insulin secretion in sheep

1988 ◽  
Vol 254 (3) ◽  
pp. R518-R523 ◽  
Author(s):  
S. Oda ◽  
A. Hagino ◽  
A. Ohneda ◽  
Y. Sasaki ◽  
T. Tsuda
Keyword(s):  
Insulin Secretion ◽  
Intravenous Infusion ◽  
Glucagon Secretion ◽  
Receptor Activation ◽  
Plasma Glucagon ◽  
Epinephrine Infusion ◽  
Plasma Insulin Concentration ◽  
Pancreatic Glucagon ◽  
Adrenergic Modulation ◽  
Glucagon And Insulin

The effect of intravenous infusion of epinephrine, either alone or together with various doses of phentolamine or propranolol, on the secretion of both glucagon and insulin was determined in six sheep. Intravenous infusion of epinephrine alone caused increases in plasma glucagon and glucose concentrations and produced a slight but significant decrease in plasma insulin concentration. The concomitant infusion of propranolol and epinephrine augmented glucagon release and inhibited insulin secretion. Combined propranolol plus epinephrine infusion also caused a marked hyperglycemia. The concomitant infusion of phentolamine and epinephrine produced slight inhibition of glucagon secretion and markedly promoted insulin secretion. Epinephrine-induced hyperglycemia was eliminated by phentolamine infusion. The effects of isoproterenol infusion on plasma glucagon, insulin, and glucose concentrations were similar to that caused by the concomitant infusion of phentolamine and epinephrine. The effects of isoproterenol were abolished by the infusion of propranolol. It is concluded that an alpha-receptor mechanism is the most important component of adrenergic modulation of pancreatic glucagon secretion, whereas beta-receptor activation stimulates and alpha-receptor activation inhibits insulin secretion in sheep.

scholarly journals Somatostatin Inhibits Insulin and Glucagon Secretion via Two Receptor Subtypes: An in Vitro Study of Pancreatic Islets from Somatostatin Receptor 2 Knockout Mice*

Endocrinology ◽  
2000 ◽  
Vol 141 (1) ◽  
pp. 111-117 ◽  
Author(s):  
M. Z. Strowski ◽  
R. M. Parmar ◽  
A. D. Blake ◽  
J. M. Schaeffer
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Somatostatin Receptor ◽  
Glucagon Secretion ◽  
Endocrine Function ◽  
Receptor Subtype ◽  
Glucagon Release ◽  
Glucagon And Insulin

Abstract Somatostatin (SST) potently inhibits insulin and glucagon release from pancreatic islets. Five distinct membrane receptors (SSTR1–5) for SST are known, and at least two (SSTR2 and SSTR5) have been proposed to regulate pancreatic endocrine function. Our current understanding of SST physiology is limited by the receptor subtype selectivity of peptidyl SST analogs, making it difficult to assign a physiological function to an identified SST receptor subtype. To better understand the physiology of SSTRs we studied the in vitro effects of potent subtype-selective nonpeptidyl SST analogs on the regulation of pancreatic glucagon and insulin secretion in wild-type (WT) and in somatostatin receptor 2 knockout (SSTR2KO) mice. There was no difference in basal glucagon and insulin secretion between islets isolated from SSTR2KO and WT mice; however, potassium/arginine-stimulated glucagon secretion was approximately 2-fold higher in islets isolated from SSTR2KO mice. Neither SST nor any SSTR-selective agonist inhibited basal glucagon or insulin release. SST-14 potently inhibited stimulated glucagon secretion in islets from WT mice and much less effectively in islets from SSTR2KO mice. The SSTR2 selective analog L-779,976 inhibited glucagon secretion in islets from WT, but was inactive in islets from SSTR2KO mice. L-817,818, an SSTR5 selective analog, slightly reduced glucagon release in both animal groups, whereas SSTR1, -3, and -4 selective analogs were inactive. SST and L-817,818 inhibited glucose stimulated insulin release in islets from WT and SSTR2KO mice. L-779,976 much less potently reduced insulin secretion from WT islets. In conclusion, our data demonstrate that SST inhibition of glucagon release in mouse islets is primarily mediated via SSTR2, whereas insulin secretion is regulated primarily via SSTR5.

scholarly journals GIP mediates the incretin effect and glucose tolerance by dual actions on α cells and β cells

2021 ◽  
Vol 7 (11) ◽  
pp. eabf1948
Author(s):  
K. El ◽  
S. M. Gray ◽  
M. E. Capozzi ◽  
E. R. Knuth ◽  
E. Jin ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Nutrient Intake ◽  
Cell Communication ◽  
Glucagon Secretion ◽  
Optimal Level ◽  
Β Cells ◽  
Β Cell ◽  
Postprandial State ◽  
Glucagon And Insulin

Glucose-dependent insulinotropic polypeptide (GIP) communicates nutrient intake from the gut to islets, enabling optimal levels of insulin secretion via the GIP receptor (GIPR) on β cells. The GIPR is also expressed in α cells, and GIP stimulates glucagon secretion; however, the role of this action in the postprandial state is unknown. Here, we demonstrate that GIP potentiates amino acid–stimulated glucagon secretion, documenting a similar nutrient-dependent action to that described in β cells. Moreover, we demonstrate that GIP activity in α cells contributes to insulin secretion by invoking paracrine α to β cell communication. Last, specific loss of GIPR activity in α cells prevents glucagon secretion in response to a meal stimulus, limiting insulin secretion and driving glucose intolerance. Together, these data uncover an important axis by which GIPR activity in α cells is necessary to coordinate the optimal level of both glucagon and insulin secretion to maintain postprandial homeostasis.

Effects of intravenous infusion of 17 amino acids on the secretion of GH, glucagon, and insulin in sheep

1991 ◽  
Vol 260 (1) ◽  
pp. E21-E26 ◽  
Author(s):  
T. Kuhara ◽  
S. Ikeda ◽  
A. Ohneda ◽  
Y. Sasaki
Keyword(s):  
Amino Acids ◽  
Insulin Secretion ◽  
Amino Acid ◽  
Aspartic Acid ◽  
Intravenous Infusion ◽  
Glucagon Secretion ◽  
Gh Secretion ◽  
Insulin And Glucagon Secretion ◽  
Igf I ◽  
Glucagon And Insulin

The effects of intravenous infusion of 17 amino acids, each at a dose of 3 mmol/kg over 30 min, on the secretion of insulin, glucagon, and growth hormone (GH) were studied in 6 castrated male sheep. Insulin-like growth factor I (IGF-I) secretion was also studied using eight of the amino acids. Plasma alpha-amino nitrogen reached a peak at 30 min followed by a gradual decrease thereafter. The greatest increase was obtained using aspartic acid and the smallest with methionine, responses to the remaining amino acids lying between these two. Leucine was the most effective amino acid in stimulating insulin secretion but did not produce any increase in glucagon and GH secretion. Alanine, glycine, and serine induced a greater enhancement of both glucagon and insulin secretion than other amino acids. No amino acid was able to specifically stimulate glucagon secretion without also increasing insulin or GH secretion. With regard to insulin and glucagon secretion, amino acids could be divided into groups according to their R groups. Neutral straight-chain amino acids stimulated both insulin and glucagon secretion, with a greater secretory response to shorter C-chain amino acids. Branched-chain amino acids tended to enhance insulin and suppress glucagon secretion. Acidic amino acids caused an increase in GH secretion. Aspartic acid caused the strongest stimulation of GH secretion, exceeding that induced by arginine. No changes in plasma IGF-I were brought about by any of the amino acids tested.

scholarly journals Inhibition of the malate–aspartate shuttle in mouse pancreatic islets abolishes glucagon secretion without affecting insulin secretion

2015 ◽  
Vol 468 (1) ◽  
pp. 49-63 ◽  
Author(s):  
Jelena A. Stamenkovic ◽  
Lotta E. Andersson ◽  
Alice E. Adriaenssens ◽  
Annika Bagge ◽  
Vladimir V. Sharoyko ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Glucagon Secretion ◽  
Nutrient Sensing ◽  
Β Cells ◽  
Mouse Pancreatic Islets ◽  
Glucagon And Insulin ◽  
Malate Aspartate Shuttle

Secretion of both glucagon and insulin is perturbed in Type 2 diabetes (T2D). In the present study, we identify a difference in mitochondrial shuttling between α- and β-cells that adjusts nutrient sensing and which potentially could be employed to specifically target secretion of either hormone.

Pancreastatin inhibits insulin secretion and stimulates glucagon secretion in mice

Diabetes ◽  
1988 ◽  
Vol 37 (3) ◽  
pp. 281-285 ◽  
Author(s):  
B. Ahren ◽  
S. Lindskog ◽  
K. Tatemoto ◽  
S. Efendic
Keyword(s):  
Insulin Secretion ◽  
Glucagon Secretion

Inhibition of Glucagon and Insulin Secretion by Somatostatin in the Rat Pancreas Perfusedin Situ

Endocrinology ◽  
1975 ◽  
Vol 96 (2) ◽  
pp. 370-374 ◽  
Author(s):  
D. G. JOHNSON ◽  
J. W ENSINCK ◽  
D. KOERKER ◽  
J. PALMER ◽  
J. GOODNER
Keyword(s):  
Insulin Secretion ◽  
Rat Pancreas ◽  
Glucagon And Insulin

scholarly journals Nitric oxide inhibits, and carbon monoxide activates, islet acid α-glucoside hydrolase activities in parallel with glucose-stimulated insulin secretion

2006 ◽  
Vol 190 (3) ◽  
pp. 681-693 ◽  
Author(s):  
Henrik Mosén ◽  
Albert Salehi ◽  
Ragnar Henningsson ◽  
Ingmar Lundquist
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Insulin Secretion ◽  
Insulin Release ◽  
Islets Of Langerhans ◽  
Direct Effect ◽  
Appreciable Effect ◽  
Intact Mouse ◽  
Glucose Stimulated Insulin Secretion ◽  
Glucoside Hydrolases

We have studied the influence of nitric oxide (NO) and carbon monoxide (CO), putative messenger molecules in the brain as well as in the islets of Langerhans, on glucose-stimulated insulin secretion and on the activities of the acid α-glucoside hydrolases, enzymes which we previously have shown to be implicated in the insulin release process. We have shown here that exogenous NO gas inhibits, while CO gas amplifies glucose-stimulated insulin secretion in intact mouse islets concomitant with a marked inhibition (NO) and a marked activation (CO) of the activities of the lysosomal/vacuolar enzymes acid glucan-1,4-α-glucosidase and acid α-glucosidase (acid α-glucoside hydrolases). Furthermore, CO dose-dependently potentiated glucose-stimulated insulin secretion in the range 0.1–1000 μM. In intact islets, the heme oxygenase substrate hemin markedly amplified glucose-stimulated insulin release, an effect which was accompanied by an increased activity of the acid α-glucoside hydrolases. These effects were partially suppressed by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. Hemin also inhibited inducible NO synthase (iNOS)-derived NO production probably through a direct effect of CO on the NOS enzyme. Further, exogenous CO raised the content of both cGMP and cAMP in parallel with a marked amplification of glucose-stimulated insulin release, while exogenous NO suppressed insulin release and cAMP, leaving cGMP unaffected. Emiglitate, a selective inhibitor of α-glucoside hydrolase activities, was able to markedly inhibit the stimulatory effect of exogenous CO on both glucose-stimulated insulin secretion and the activityof acid glucan-1,4-α-glucosidase and acid α-glucosidase, while no appreciable effect on the activities of other lysosomal enzyme activities measured was found. We propose that CO and NO, both produced in significant quantities in the islets of Langerhans, have interacting regulatory roles on glucose-stimulated insulin secretion. This regulation is, at least in part, transduced through the activity of cGMP and the lysosomal/vacuolar system and the associated acid α-glucoside hydrolases, but probably also through a direct effect on the cAMP system.

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