DEVELOPMENT OF PATHWAYS OF INSULIN SECRETION IN THE RABBIT

1975 ◽  
Vol 64 (2) ◽  
pp. 349-361 ◽  
Author(s):  
R. D. G. MILNER ◽  
F. N. LEACH ◽  
M. A. ASHWORTH ◽  
A. CSER ◽  
P. M. B. JACK
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Similar Rate ◽  
Extracellular Glucose ◽  
Cell Changes ◽  
Foetal Pancreas ◽  
Stimulation Of

SUMMARY Insulin release was studied in vitro using pieces of pancreas from rabbits of between 24 days gestational age and 6 weeks postnatal age. When allowance was made for the fraction of pancreas which was endocrine, 16·5 mm-glucose caused increasing stimulation of insulin release as development advanced and 3·3 mm-glucose caused a similar rate of secretion at all ages. Secretion was not significantly influenced by insulin destruction in the incubation medium. Glucagon (5 μg/ml) did not stimulate insulin secretion from 24-day foetal pancreas but did so postnatally. Theophylline (1 mmol/l) stimulated insulin release at all ages and was equipotent on 24-day foetal pancreas in 3·3 or 16·5 mm-glucose. The stimulation of insulin release from 24-day foetal pancreas by 1 mm-theophylline occurred in the absence of extracellular glucose, pyruvate, fumarate and glutamate and in the presence of mannoheptulose and 2-deoxyglucose (each 3 mg/ml). Adrenaline (1 μmol/l) and diazoxide (250 μg/ml) abolished or attenuated the stimulation of insulin release by glucose, leucine plus arginine or theophylline from 24-day foetal, 1 day and 6 weeks postnatal pancreas. The stimulation of insulin release from 6-week-old pancreas by 1 mm-barium was blocked by adrenaline and diazoxide but the effect became less with increasing immaturity. The experimental results illustrate some of the ways in which insulin secretion by the rabbit β cell changes as a function of development and draw attention to the importance of glucose and cyclic adenosine monophosphate in this process.

HUMAN FOETAL PANCREATIC INSULIN SECRETION IN RESPONSE TO IONIC AND OTHER STIMULI

1971 ◽  
Vol 51 (2) ◽  
pp. 323-332 ◽  
Author(s):  
R. D. G. MILNER ◽  
A. J. BARSON ◽  
M. A. ASHWORTH
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Β Cells ◽  
Pancreatic Insulin ◽  
Foetal Life ◽  
Acinar Tissue ◽  
Foetal Pancreas

SUMMARY Pieces of human foetal pancreas were incubated under control conditions and in media containing different stimuli of insulin release. Insulin secretion was stimulated from the pancreases of foetuses (83–625 g body weight) which were of 16–24 weeks gestational age. Potassium (60 mmol/l), barium (2·54 mmol/l) and ouabain (10−5 mol/l) were effective stimuli in all experiments. Glucagon (5 μg/ml), theophylline (1 mmol/l) and dibutyryl 3′,5′-cyclic adenosine monophosphate (1 mmol/l) stimulated insulin secretion in media containing 0, 0·6 or 3·0 mg glucose/ml. Theophylline and dibutyryl 3′,5′-cyclic adenosine monophosphate were effective in all experients and glucagon stimulated insulin release in four out of six experiments. At all ages studied, histological examination of the pancreas after each experiment revealed islets of Langerhans containing β cells. In most cases the islets were of the mantle type but occasionally bipolar islets were seen. Cellular normality, as judged by light microscopy, was preserved after periods of incubation for up to 5½ h. Glycogen was demonstrable in the pancreatic acinar tissue but not in the islets. The results of these experiments indicate that, between the 16th and 24th week of foetal life, the human β cell is capable of releasing insulin in vitro when stimulated appropriately.

Direct effect of parathyroid hormone on insulin secretion from pancreatic islets

1990 ◽  
Vol 258 (6) ◽  
pp. E975-E984 ◽  
Author(s):  
G. Z. Fadda ◽  
M. Akmal ◽  
L. G. Lipson ◽  
S. G. Massry
Keyword(s):  
Insulin Secretion ◽  
Parathyroid Hormone ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Direct Effect ◽  
Indirect Evidence ◽  
Cytosolic Calcium ◽  
Dependent Manner ◽  
Stimulation Of

Indirect evidence indicates that parathyroid hormone (PTH) interacts with pancreatic islets and modulates their insulin secretion. This property of PTH has been implicated in the genesis of impaired insulin release in chronic renal failure. We examined the direct effect of PTH-(1-84) and PTH-(1-34) on insulin release using in vitro static incubation and dynamic perifusion of pancreatic islets from normal rats. Both moieties of the hormone stimulated in a dose-dependent manner glucose-induced insulin release but higher doses inhibited glucose-induced insulin release. This action of PTH was modulated by the calcium concentration in the media. The stimulatory effect of PTH was abolished by its inactivation and blocked by its antagonist [Tyr-34]bPTH-(7-34)NH2. PTH also augmented phorbol ester (TPA)-induced insulin release, stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation by pancreatic islets, and significantly increased (+50 +/- 2.7%, P less than 0.01) their cytosolic calcium. Verapamil inhibited the stimulatory effect of PTH on insulin release. The data show that 1) pancreatic islets are a PTH target and may have PTH receptors, 2) stimulation of glucose-induced insulin release by PTH is mediated by a rise in cytosolic calcium, 3) stimulation of cAMP production by PTH and a potential indirect activation of protein kinase C by PTH may also contribute to the stimulatory effect on glucose-induced insulin release, and 4) this action of PTH requires calcium in incubation or perifusion media.

scholarly journals Islet-cell metabolism during insulin release. Effects of glucose, citrate, octanoate, tolbutamide, glucagon and theophylline

1969 ◽  
Vol 115 (2) ◽  
pp. 257-262 ◽  
Author(s):  
W Montague ◽  
K W Taylor
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Islet Cell ◽  
Cell Metabolism ◽  
Inhibitory Effect ◽  
Linear Increase ◽  
Intracellular Concentration ◽  
Extracellular Glucose ◽  
Oxidation Of Glucose

1. Concentrations of glucose 6-phosphate and 6-phosphogluconate were studied in islets of Langerhans isolated from rat pancreas and incubated in the presence of various agents that induce insulin release. 2. In response to rising concentrations of extracellular glucose (2–10mm) there is a linear increase in the intracellular concentration of glucose 6-phosphate, though this is not the case for 6-phosphogluconate, the intracellular concentration of which only increases when the external glucose concentration exceeds 5mm. 3. Tolbutamide, octanoate and citrate, all of which promote insulin secretion from isolated islets, increase the intracellular concentrations of glucose 6-phosphate and 6-phosphogluconate. The results obtained in the presence of octanoate and citrate are compatible with an inhibitory effect of citrate on islet-cell phosphofructokinase. 4. Theophylline and glucagon when incubated with islets in vitro promote insulin release and cause a rise in 6-phosphogluconate concentration and not in that of glucose 6-phosphate. 5. It is suggested that the further metabolism of glucose 6-phosphate through a pathway other than glycolysis is essential for insulin release. One such pathway involves its oxidation to 6-phosphogluconate, which seems to be a necessary accompaniment of insulin secretion due to glucose. The possibility that agents other than glucose promote insulin release by enhancing the oxidation of glucose 6-phosphate through this pathway is discussed.

scholarly journals In Vitro and In Vivo Effects of Palmaria palmata Derived Peptides on Glucose Metabolism

2021 ◽  
Author(s):  
Pádraigín A. Harnedy-Rothwell ◽  
Chris M. McLaughlin ◽  
Aurélien V. Le Gouic ◽  
Ciaran Mullen ◽  
Vadivel Parthsarathy ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Control ◽  
Protein Hydrolysate ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Antidiabetic Activity ◽  
Palmaria Palmata ◽  
Glucagon Like Peptide 1

AbstractThree synthetic peptides, ILAP, LLAP and MAGVDHI, derived from a Palmaria palmata protein hydrolysate were assessed for their antidiabetic potential in vitro and in vivo. In addition to inhibiting dipeptidyl peptidase-IV in a cell-based in situ assay all three peptides significantly increased the half-life of the incretin hormone glucagon-like peptide-1 (GLP-1). ILAP and LLAP mediated a significant increase (p < 0.001) in insulin secretion from BRIN-BD11 cells compared to the glucose control, while MAGVDHI had no insulinotropic activity at an eqimolar concentration (10–6 M). A significant increase in the concentration of cyclic adenosine monophosphate production in BRIN-BD11 cells mediated by ILAP (p < 0.001) and LLAP (p < 0.01) compared to the basal control, would indicate that insulin secretion may be mediated by membrane based activation. Furthermore, ILAP and LLAP acted as glucose-dependent insulinotropic polypeptide (GIP) secretagogues, stimulating a significant increase (p < 0.01) in the concentration of GIP released from enteroendocrine STC-1 cells compared to the glucose control. When tested in vivo in healthy male NIH Swiss mice, ILAP and LLAP, mediated a significant increase (p < 0.01) in plasma insulin and decrease (p < 0.05) in blood glucose, respectively, compared to the control. MAGVDHI mediated a significant (p < 0.001) sustained reduction in food intake in food deprived trained mice. These results demonstrate that the Palmaria palmata peptides studied herein have prospective antidiabetic activity and have the potential to act as agents that can be used alone or in combination with drugs, to aid in the prevention and management of Type 2 diabetes mellitus.

scholarly journals Studies with the Cyclic Adenosine Monophosphate Receptor and Stimulation of in Vitro Transcription of the Gal Operon

1974 ◽  
Vol 249 (11) ◽  
pp. 3592-3596
Author(s):  
Wayne B. Anderson ◽  
Max E. Gottesman ◽  
Ira Pastan
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
In Vitro Transcription ◽  
Stimulation Of

Effect of gastrin-releasing peptide on the secretion of mouse islet hormones in vitro

1990 ◽  
Vol 127 (2) ◽  
pp. 335-340 ◽  
Author(s):  
L. C. Wilkes ◽  
C. J. Bailey ◽  
M. G. Thompson ◽  
J. M. Conlon ◽  
K. D. Buchanan
Keyword(s):  
Insulin Release ◽  
Pancreatic Polypeptide ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Second Phase ◽  
Rinm5f Cells ◽  
Maximum Increase ◽  
Gastrin Releasing Peptide ◽  
Mouse Islets

ABSTRACT Collagenase-isolated mouse islets were incubated with gastrin-releasing peptide (GRP). At 5·6 mmol glucose/1, 10 nmol GRP/l increased the release of insulin (by 50%) and glucagon (by twofold), decreased the release of pancreatic polypeptide (by 35%), but did not significantly affect the release of somatostatin. At 16·7 mmol glucose/l, 10 nmol GRP/l increased glucagon release (by fivefold) and decreased pancreatic polypeptide release (by 46%), without significantly altering insulin and somatostatin release. GRP (200 nmol/l) did not affect insulin release by perifused mouse islets at 2·8 mmol glucose/l, but increased both first and second phase insulin release after a square wave increase in the glucose concentration to 11·1 mmol/l. At 5·6 mmol glucose/l, GRP (100 pmol/1–100 nmol/l) increased (by 50–70%) insulin release by the RINm5F clonal cell line. GRP did not affect glucose oxidation or the cyclic adenosine monophosphate content of RINm5F cells. However, the intracellular free Ca2+ concentration of RINm5F cells was rapidly and transiently increased by GRP (maximum increase of 64% about 10 s after exposure to 1 μmol GRP/l). The rise of intracellular free Ca2+ was approximately halved in the absence of extracellular Ca2+. The results suggest that GRP may contribute to the normal regulation of the endocrine pancreas. The insulin-releasing effect of GRP is mediated via increased cytosolic free Ca2+, derived both from an increased net influx of extracellular Ca2+ and from mobilization of intracellular Ca2+ stores. Journal of Endocrinology (1990) 127, 335–340

Effect of synthetic C-terminal fragments of hGH on insulin release by isolated islets.

1978 ◽  
Vol 234 (5) ◽  
pp. E527
Author(s):  
C Weerasinghe ◽  
J Bornstein
Keyword(s):  
Insulin Release ◽  
Glucose Measurement ◽  
Isolated Rat Islets ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose ◽  
In Vitro Effects ◽  
Rat Islets Of Langerhans ◽  
Camp Levels ◽  
Stimulation Of

Synthetic fragments representing the C-terminal end of the growth hormone molecule have been tested for their direct in vitro effects on insulin release by isolated rat islets of Langerhans. hGH 177-191 caused a dose-related potentiation of glucose-induced insulin release, whereas the peptide by itself caused no stimulation of insulin release from the islets. The rate curves constructed for insulin secretion as a function of extracellular glucose concentration showed that the Km for glucose is not altered in the presence of the peptide, but that the Vmax of secretion is increased. Significant potentiation of insulin release by the peptide was seen only at high extracellular concentrations of glucose. Measurement of cAMP levels in islets showed that the peptide caused no significant alteration of cAMP levels while still potentiating insulin release. It was therefore concluded that the mechanism of potentiation of insulin release by the peptide may be independent of the changes in cAMP levels in islets. hGH 172-191, too, caused potentiation of glucose-stimulated insulin release from islets, whereas hGH 179-191 was not active in this report.

Dobutamine Antagonizes Epinephrine's Biochemical and Cardiotonic Effects 

1998 ◽  
Vol 89 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Richard C. Prielipp ◽  
Drew A. MacGregor ◽  
Roger L. Royster ◽  
Neal D. Kon ◽  
Michael H. Hines ◽  
...  
Keyword(s):  
Artery Bypass ◽  
Phase 1 ◽  
Human Lymphocytes ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Camp Production ◽  
Isobolographic Analysis ◽  
Camp Generation ◽  
Vitro Model

Background Patients may receive more than one positive inotropic drug to improve myocardial function and cardiac output, with the assumption that the effects of two drugs are additive. The authors hypothesized that combinations of dobutamine and epinephrine would produce additive biochemical and hemodynamic effects. Methods The study was performed in two parts. Phase 1 used human lymphocytes in an in vitro model of cyclic adenosine monophosphate (cAMP) generation in response to dobutamine (10(-8) to 10(-4) M) or epinephrine (10(-9) M to 10(-5) M), and dobutamine and epinephrine together. Phase 2 was a clinical study in patients after aortocoronary artery bypass in which isobolographic analysis compared the cardiotonic effects of dobutamine (1.25, 2.5, or 5 microg x kg(-1) x min(-1)) or epinephrine (10, 20, or 40 ng x kg(-l) x min(-1)), alone or in combination. Results In phase 1, dobutamine increased cAMP production 41%, whereas epinephrine increased cAMP concentration approximately 200%. However, when epinephrine (10(-6) M) and dobutamine were combined, dobutamine reduced cAMP production at concentrations between 10(-6) to 10(-4) M (P = 0.001). In patients, 1.25 to 5 microg x kg(-1) x min(-1) dobutamine increased the cardiac index (CI) 15-28%. Epinephrine also increased the CI with each increase in dose. However, combining epinephrine with the two larger doses of dobutamine (2.5 and 5microg x kg(-1) x mi(-1)) did not increase the CI beyond that achieved with epinephrine and the lowest dose of dobutamine (1.25 microg x kg(-1) x min(-1)). In addition, the isobolographic analysis for equieffective concentrations of dobutamine and epinephrine suggests subadditive effects. Conclusions Dobutamine inhibits epinephrine-induced production of cAMP in human lymphocytes and appears to be subadditive by clinical and isobolographic analyses of the cardiotonic effects. These findings suggest that combinations of dobutamine and epinephrine may be less than additive.

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