Regulation of glucagon release: Effects of insulin on the pancreatic A2-cell of the guinea pig

Östenson, Claes‐Göran

doi:10.1007/bf01235889

Cited by 59 publications

(36 citation statements)

References 45 publications

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“…The observed elevation of insulin and suppression of glucagon in response to high [K +] has been reported by us previously [3]; the reverse effect obtained with low [K +] is now reported for the first time. While correlation data, such as we have obtained, may be consistent with the hypothesized intraislet regulation of glucagon secretion by insulin [9], the data alone are not sufficient to establish such a relationship. In fact, such a mechanism does not appear to be well supported either in the literature or by our findings.…”

Section: Discussioncontrasting

confidence: 60%

Potassium ion concentration alters glucagon secretion independently of insulin secretion in the isolated rat pancreas

et al. 1982

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Summary. In the arginine-stimulated perfused rat pancreas, elevated concentrations of potassium ion inhibited glucagon secretion while stimulating the secretion of insulin. Decreased potassium ion produced the reverse effect. The observed inverse correlation between changes in insulin and glucagon secretion (r = -0.64; p < 0.001) was suggestive of local interactions between islet hormones, and prompted us to determine whether potassium-induced changes in glucagon secretion were dependent upon concurrent changes in insulin release. We found that when insulin secretion was greatly suppressed, either through acute induction of diabetes with streptozotocin or by utilization of a glucose-free perfusate, no qualitative differences in glucagon responsiveness to altered potassium ion were evident, although the amplitude of these glucagon changes was enhanced. Similarly, when exogenous insulin (20,000 mU/1) was added to the perfusate in order to render potassium-induced changes in endogenous insulin secretion insignificant, glucagon responsiveness to altered potassium ion was maintained. Exogenous insulin alone had no effect on arginine-stimulated glucagon secretion. We conclude that any indirect effects of potassium ion on arginine-stimulated glucagon secretion are not mediated by insulin, but could be related to changes in somatostatin secretion.

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Section: Discussioncontrasting

confidence: 60%

Potassium ion concentration alters glucagon secretion independently of insulin secretion in the isolated rat pancreas

et al. 1982

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“…Relationship between glucose-regulated glucagon, insulin and somatostatin secretion Since glucose control of glucagon secretion has been suggested to involve paracrine release of insulin [17][18][19][20][21][22], GABA [22][23][24] and Zn 2+ [25,26] from the beta cells, and somatostatin from the delta cells [18,27], we studied how the glucose concentration affected the release of hormones from mouse islets. Glucagon secretion was inhibited by glucose in the 4 to 20 mmol/l range with maximal effect at 7 mmol/l (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…One involves direct effects of glucose on the alpha cell [8][9][10][11][12][13][14][15][16][17]. Another is based on an indirect action mediated by release of insulin [17][18][19][20][21][22], γ-aminobutyric acid (GABA) [22][23][24], Zn 2+ [25,26] or somatostatin [18,27]. A third predicts that glucose sensing occurs in the hypothalamus with altered neural signalling to alpha cells [28].…”

Section: Introductionmentioning

confidence: 99%

Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells

2006

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Aims/hypothesis The mechanisms by which glucose regulates glucagon release are poorly understood. The present study aimed to clarify the direct effects of glucose on the glucagon-releasing alpha cells and those effects mediated by paracrine islet factors. Materials and methods Glucagon, insulin and somatostatin release were measured from incubated mouse pancreatic islets and the cytoplasmic Ca 2+ concentration ([Ca 2+ ] i ) recorded in isolated mouse alpha cells. Results Glucose inhibited glucagon release with maximal effect at 7 mmol/l. Since this concentration corresponded to threshold stimulation of insulin secretion, it is unlikely that inhibition of glucagon secretion is mediated by beta cell factors. Although somatostatin secretion data seemed consistent with a role of this hormone in glucose-inhibited glucagon release, a somatostatin receptor type 2 antagonist stimulated glucagon release without diminishing the inhibitory effect of glucose. In islets exposed to tolbutamide plus 8 mmol/l K + , glucose inhibited glucagon secretion without stimulating the release of insulin and somatostatin, indicating a direct inhibitory effect on the alpha cells that was independent of ATP-sensitive K + channels. Glucose lowered [Ca 2+ ] i of individual alpha cells independently of somatostatin and beta cell factors (insulin, Zn 2+ and γ-aminobutyric acid). Glucose suppression of glucagon release was prevented by inhibitors of the sarco(endo)plasmic reticulum Ca 2+ -ATPase, which abolished the [Ca 2+ ] i -lowering effect of glucose on isolated alpha cells. Conclusions/interpretation Beta cell factors or somatostatin do not seem to mediate glucose inhibition of glucagon secretion. We instead propose that glucose has a direct inhibitory effect on mouse alpha cells by suppressing a depolarising Ca 2+ store-operated current.

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“…Since the efferent capillaries pass through the non-B cells and merge into collecting venules outside the islets, a high insulin concentration in the effluent blood might have a modulating effect on glucagon release from the A cells. Such effects of insulin have previously been demonstrated in vivo [33] and in vitro [34,35] and may explain the increased circulating glucagon levels seen in insulin deficiency [34]. The regulation of islet blood flow has become accessible to investigation relatively recently.…”

Section: The Blood Supply Of the B Cellmentioning

confidence: 90%

The life story of the pancreatic B cell

Hellerström

1984

Diabetologia

115

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Summary. Most research on the pancreatic B cell has so far focussed on the regulation and molecular biology of insulin biosynthesis and release. The present review draws attention to some additional areas of islet research which have become accessible to investigation by recent methodological progress and which may advance our understanding of the role of the B cell in diabetes. There is now evidence to suggest that B cells arise from a pool of undifferentiated precursor cells in the fetal and newborn pancreas. These ceils may contribute to islet growth and, if inappropriately stimulated, also to early islet hyperplasia. In the postnatal state, B-cell function is finely tuned by a complex set of incoming signals, one of which is the nutrient supply provided by the blood. Recent studies indicate that a disproportionately high fraction of pancreatic blood is diverted to the islets and that the islet blood flow is increased by glucose. An acute stimulus to insulin release may thus be accompanied by a process which enhances the distribution of the hormone to the target cells. Long-term adjustments of B-cell function are made by changes in B-cell number and total mass. Adaptive growth responses to an increased insulin demand occur in a number of hereditary diabetic syndromes in animals, but in some of these there is an inherited restriction on the capacity for B-cell proliferation leading to further deterioration of the glucose tolerance. Some evidence suggests that a similar mechanism may operate also in human non-insulin-dependent diabetes. A critical appraisal of this hypothesis requires, however, that human B cells should be tested for their growth characteristics. Studies of B-cell proliferation in experimental animals have shown that the B cell passes through the cell cycle at a relatively high rate but that the fraction of proliferating cells is low. Regulation of growth of the total B-cell mass seems to take place by changes in the number of B cells passing through the cell cycle rather than by changes in the rate of the cycle. The number of proliferating B cells also shows a marked decrease with age. It is at present uncertain to what extent these regulatory mechanisms apply also to the human B cell but it can be anticipated that further technical developments will elucidate this problem.

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Regulation of glucagon release: Effects of insulin on the pancreatic A2-cell of the guinea pig

Cited by 59 publications

References 45 publications

Potassium ion concentration alters glucagon secretion independently of insulin secretion in the isolated rat pancreas

Potassium ion concentration alters glucagon secretion independently of insulin secretion in the isolated rat pancreas

Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells

The life story of the pancreatic B cell

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