Glucagon and Insulin Secretion

Samols, Ellis

doi:10.1007/978-3-642-68866-9_22

Cited by 40 publications

(46 citation statements)

References 127 publications

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“…Therefore, the present results indicate that exogenous insulin is needed for the suppression of glucagon release under experimental conditions. This is essentially consistent with the known effects of insulin infusions into the superior pancreaticoduodenal artery of normal dogs (Samols et al 1972) and insulin infusions of isolated perfused normal rat pancreas (Unger and Lefebvre 1972). The results are also consistent with the suppression of glucagon release by exogenous insulin in diabetic dogs (Braaten et al 1974) and diabetic man (Raskin et al 1975).…”

Section: Discussionsupporting

confidence: 87%

“…The antiserum KF-15 is specific for the C-terminal fragment of pancreatic glucagon (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29).…”

Section: Assaysmentioning

confidence: 99%

“…In the normal pancreas, it is possible that Ca2+ deprivation may interfere with the secretion of insulin (Curry et al 1968). As a result, this change in insulin secretion possibly increases glucagon release (Maruyama et al 1984; Samols et al 1972). Thus, it is important to exclude the influence of endogenous insulin on alpha cell function when the role of Ca2+ in the secretooy process of glucagon is investigated.…”

mentioning

confidence: 99%

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Role of calcium in suppression of glucagon release from isolated diabetic rat pancreata.

Fujita

Kawaji

Moriya

et al. 1988

Tohoku J. Exp. Med.

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Section: Discussionsupporting

confidence: 87%

“…The antiserum KF-15 is specific for the C-terminal fragment of pancreatic glucagon (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29).…”

Section: Assaysmentioning

confidence: 99%

mentioning

confidence: 99%

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Role of calcium in suppression of glucagon release from isolated diabetic rat pancreata.

Fujita

Kawaji

Moriya

et al. 1988

Tohoku J. Exp. Med.

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“…The decrement in insulin release from ␤-cells has been proposed to signal the ␣-cell to release glucagon (1)(2)(3). Recently, we demonstrated this phenomenon directly in vivo in streptozotocin-induced diabetic rats and in vitro using isolated islets from these animals.…”

mentioning

confidence: 69%

Zinc, Not Insulin, Regulates the Rat α-Cell Response to Hypoglycemia In Vivo

et al. 2007

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The intraislet insulin hypothesis proposes that the decrement in ␤-cell insulin secretion during hypoglycemia provides an activation signal for ␣-cells to release glucagon. A more recent hypothesis proposes that zinc atoms suppress glucagon secretion via their ability to open ␣-cell ATPsensitive K ؉ channels. Since insulin binds zinc, and zinc is cosecreted with insulin, we tested whether decreased zinc delivery to the ␣-cell activates glucagon secretion. In streptozotocin-induced diabetic Wistar rats, we observed that switching off intrapancreatic artery insulin infusions in vivo during hypoglycemia greatly improved glucagon secretion (area under the curve [AUC]: control group 240 ؎ 261 and experimental group 4,346 ؎ 1,259 pg ⅐ ml ؊1 ⅐ 90 min ؊1 ; n ‫؍‬ 5, P < 0.02). Switching off pancreatic artery infusions of zinc chloride during hypoglycemia also improved the glucagon response (AUC: control group 817 ؎ 107 and experimental group 3,445 ؎ 573 pg ⅐ ml ؊1 ⅐ 90 min ؊1 ; n ‫؍‬ 6, P < 0.01). However, switching off zinc-free insulin infusions had no effect. Studies of glucose uptake in muscle and liver cell lines verified that the zinc-free insulin was biologically active. We conclude that zinc atoms, not the insulin molecule itself, provide the switch-off signal from the ␤-cell to the ␣-cell to initiate glucagon secretion during hypoglycemia. Diabetes 56:1107-1112, 2007 G lucagon secretion into the hepatic portal circulation is critical for counterregulation of hypoglycemia by virtue of its stimulatory effect on hepatic glycogenolysis, which releases glucose into the systemic circulation to return blood glucose to normal levels. The decrement in insulin release from ␤-cells has been proposed to signal the ␣-cell to release glucagon (1-3). Recently, we demonstrated this phenomenon directly in vivo in streptozotocin-induced diabetic rats and in vitro using isolated islets from these animals. In the in vivo studies, an insulin infusion into the pancreatic artery was switched off when the animals were made hypoglycemic by a jugular-vein infusion of insulin (4).Glucagon secretion, absent in control diabetic animals, was fully restored by this maneuver. Glucagon release was not initiated by this maneuver if saline rather than insulin was used, or if insulin was infused but not switched off. The glucagon response was not observed during normoglycemic or hyperglycemic conditions; the switch-off signal was effective only in the setting of hypoglycemia. We corroborated these findings with in vitro islet perifusion studies (5).Recent work from several laboratories has demonstrated that zinc atoms are capable of suppressing ␣-cell function via activation of rat ␣-cell ATP-sensitive K ϩ (K ATP ) channels (6 -9). Since zinc atoms are bound by and cosecreted with insulin, we hypothesized that zinc might provide the switch-off signal during hypoglycemia. To evaluate this hypothesis, we performed in vivo studies using intrapancreatic artery infusions of zinc-containing insulin, zinc chloride alone, or zinc-free insulin in streptozo...

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“…On the contrary, in the hypoglycemic state, the marked attenuation of insulin results in signaling to α-cells to promote glucagon secretion (18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Decrease of γ-aminobutyric acid and zinc ions in the islet periportal circulation stimulates glucagon secretion during hypoglycemia

Jiang

Liu

et al. 2017

Exp Ther Med

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Abstract. The present study assessed the effects of γ-aminobutyric acid (GABA) from β-cells on glucose levels and glucagon secretion, and identified channels via which glucagon secretion is initiated. An in vivo experiment was performed containing three groups: Intrapancreatic artery infusion of GABA alone, GABA plus insulin or insulin alone in rats with diabetes. Rats infused with GABA and insulin were also subdivided in groups receiving additional infusion of K + -channel activator diazoxide (DIA), K + -channel blocker tolbutamide (TLB) and calcium channel blocker nifedipine (NIF). In the hypoglycemic state, termination of infusion of insulin and insulin plus GABA resulted in signaling to the α-cells to secrete glycogen, while that of GABA alone did not. However, intrapancreatic artery infusion of K + -channel activator DIA, K + -channel blocker TLB or calcium channel blocker NIF in addition to GABA and insulin had no effect on glucagon secretion. In conclusion, if the delivery of insulin or GABA plus insulin in rats with hypoglycemia is terminated, β-cells are stimulated and signal the α-cells to secrete glucagon. Thus, the detection of a sudden decrease in zinc levels by β-cells as well as a decrease in GABA in the periportal circulation induces signaling to α-cells to stimulate them to secrete glucagon. IntroductionTreatment for patients with type 1 or advanced type 2 diabetes by use of exogenous insulin places them at high risk for hypoglycemia. The physiological response to hypoglycemia involves multiple intrinsic defense mechanisms, which consists of input signals sent by the central nervous system and release of epinephrine, glucagon, cortisol and growth hormone. A chief mechanism among these is the increase in glucagon secretion. In patients with diabetes, the counter-regulatory glucagon response is severely compromised. Numerous in vitro and in vivo studies have proposed that insulin, Zn 2+ , γ-aminobutyric acid (GABA) and somatostatin exerts a paracrine control on glucagon secretion under certain conditions (1,2).Within the islets, the regulation of glucagon secretion by glucose and paracrine factors (i.e., β-cell secretory products) is mediated by electrical machinery comprising a variety of ion channels that determine the depolarization or hyperpolarization of α-cells (3). The intra-islet insulin hypothesis holds that upon decreasing insulin secretion by β-cells, they may send a signal to α-cells that contributes to the release of glucagon. Another hypothesis infers that glucagon secretion is inhibited by zinc ions due to their effects on adenosine triphosphate (ATP)-sensitive K + -channels of α-cells (4). In vivo studies have demonstrated that if insulin or zinc ion infusion into the pancreatic artery is performed, while animals are made hypoglycemic by an insulin infusion through the jugular vein, following the end of the infusion glucagon secretion is stimulated in animals with diabetes, but not in animals without diabetes (4-6).GABA serves as an inhibitor in the central nervous system and at hi...

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Glucagon and Insulin Secretion

Cited by 40 publications

References 127 publications

Role of calcium in suppression of glucagon release from isolated diabetic rat pancreata.

Role of calcium in suppression of glucagon release from isolated diabetic rat pancreata.

Zinc, Not Insulin, Regulates the Rat α-Cell Response to Hypoglycemia In Vivo

Decrease of γ-aminobutyric acid and zinc ions in the islet periportal circulation stimulates glucagon secretion during hypoglycemia

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