Time-Dependent Stimulation of Insulin Exocytosis by 3′,5′-Cyclic Adenosine Monophosphate in the Rat Islet β-Cell

Yamada, Satoko; Komatsu, Mitsuhisa; Sato, Yoshihiko; Yamauchi, Kazuyo; Kojima, Itaru; Aizawa, Toru; Hashizume, Kiyoshi

doi:10.1210/en.2002-220368

Cited by 26 publications

(20 citation statements)

References 48 publications

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“…As suggested by this finding, cAMP strongly augments the K ATP channelindependent, Ca 2+ -independent, insulinotropic actions of glucose (Fig. 1) [37,38]. The interactions of PKC, a mediator of acetylcholine-induced insulin release, and Ca 2+ signals are different in that PKC activators robustly augment Ca 2+ -stimulated insulin release even in the absence of glucose, suggesting a direct interaction.…”

Section: Mechanisms Of Insulin Secretion Frommentioning

confidence: 65%

Glucose-incretin interaction revisited [Review]

et al. 2011

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Abstract. Pancreatic beta cell dysfunction is pivotal to the development of diabetes, and restoration of insulin action is of primary importance. Here, we present a review of the mechanism of insulin secretion by pancreatic beta cells and discuss the mutual interaction of signaling pathways in stimulus-secretion coupling to better understand the scientific basis of pharmacological treatment for insulin secretion deficiency. Glucose stimulates insulin secretion via membrane depolarization by closure of ATP-sensitive K + channels (K ATP channels) and opening of L-type voltage-dependent Ca 2+ channels. The resultant elevation of cytosolic free Ca 2+ triggers insulin exocytosis. This is termed the "K ATP -dependent pathway" and is shared by sulfonylurea, which closes K ATP channels. Glucose also stimulates insulin release independent of its action on K ATP channels. This is referred to as the "K ATP -independent pathway," the molecular basis of which remains elusive. In the pancreatic beta cell, incretin hormones increase cAMP level, which enhances glucose-stimulated insulin release by protein kinase A-dependent and -independent mechanisms. Importantly, cAMP does not directly augment Ca 2+-stimulated insulin release per se. The stimulatory level of ambient glucose is an absolute requirement for incretin to enhance insulin release. Therefore, incretin/cAMP enhances K ATP -independent insulinotropic action of glucose. The robust glucoselowering effect of DPP4 inhibitor add-on in diabetic patients with sulfonylurea secondary failure is intriguing. With the clinical availability of DPP4 inhibitor and GLP-1 mimetics, the importance of the interactions between cAMP signaling and K ATP channel-independent actions of glucose is reappraised.Key words: Glucose, Insulin secretion, ATP-sensitive K + channel, Incretin, cAMPInsulIn is the only hormone that lowers plasma glucose concentration. Therefore, insufficient insulin activity leads to chronic elevation of plasma glucose and diabetes mellitus, and restoration of insulin activity is vital for normalization of metabolism in diabetes.Here, we present a review of the pathophysiology of insulin deficiency in type 2 diabetes (T2D), stimulussecretion coupling in the pancreatic beta cells, and the interaction of glucose and cAMP signal to provide a comprehensive view regarding the basis of pharmacological treatment of patients with T2D.

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Section: Mechanisms Of Insulin Secretion Frommentioning

confidence: 65%

Glucose-incretin interaction revisited [Review]

et al. 2011

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“…This finding strongly indicates that incretin primes the b-cells in the presence of stimulatory ambient glucose concentration. Incretin priming occurs in a Ca 2+ -independent manner, even under stringent Ca 2+ -free conditions 31 .…”

Section: Priming Of B-cellsmentioning

confidence: 99%

Glucose‐stimulated insulin secretion: A newer perspective

Komatsu

Takei

Ishii

et al. 2013

J of Diabetes Invest

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Existing concepts and models for glucose-stimulated insulin secretion (GSIS) are overviewed and a newer perspective has been formulated toward the physiological understanding of GSIS. A conventional model has been created on the basis of in vitro data on application of a square wave high glucose in the absence of any other stimulatory inputs. Glucose elicits rapid insulin release through an adenosine triphosphate-sensitive K + channel (K ATP channel)-dependent mechanism, which is gradually augmented in a K ATP channel-independent manner. Biphasic GSIS thus occurs. In the body, the b-cells are constantly exposed to stimulatory signals, such as glucagon-like peptide 1 (GLP-1), parasympathetic inputs, free fatty acid (FFA), amino acids and slightly suprathreshold levels of glucose, even at fasting. GLP-1 increases cellular cyclic adenosine monophosphate, parasympathetic stimulation activates protein kinase C, and FFA, amino acids and glucose generate metabolic amplification factors. Plasma glucose concentration gradually rises postprandially under such tonic stimulation. We hypothesize that these stimulatory inputs together make the b-cells responsive to glucose independently from its action on K ATP channels. Robust GSIS in patients with a loss of function mutation of the sulfonylurea receptor, a subunit of K ATP channels, is compatible with this hypothesis. Furthermore, pre-exposure of the islets to an activator of protein kinase A and/or C makes b-cells responsive to glucose in a K ATP channel-and Ca 2+-independent manner. We hypothesize that GSIS occurs in islet b-cells without glucose regulation of K ATP channels in vivo, for which priming with cyclic adenosine monophosphate, protein kinase C and non-glucose nutrients are required. To understand the physiology of GSIS, comprehensive integration of accumulated knowledge is required. (J Diabetes Invest,

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“…This pharmacological tool is a direct activator of adenylate cyclase that in the absence of added nutrient has little, if any, independent stimulatory effect (Wiedenkeller & Sharp 1983, Yamada et al 2002. The addition of forskolin to the amino acid mixture significantly augmented insulin secretion from mouse islets.…”

Section: Figurementioning

confidence: 99%

Comparative effects of amino acids and glucose on insulin secretion from isolated rat or mouse islets

Zawalich

Yamazaki²,

Zawalich³

et al. 2004

Journal of Endocrinology

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Glucose and the combination of leucine and glutamine were used to stimulate insulin secretion from rat islets during a dynamic perifusion and the responses obtained were compared with those elicited from mouse islets under identical conditions. In rat islets, glucose (15 mM) or the amino acid combination of 10 mM glutamine plus 20 mM leucine were most efficacious and peak secondphase insulin release responses were 20-to 30-fold above prestimulatory rates. In contrast to rat islet responses, sustained second-phase insulin secretory responses to the same agonists were minimally increased 1-to 2-fold from mouse islets. Parallel studies demonstrated that phospholipase C (PLC) was markedly activated in rat, but not mouse, islets by both high glucose concentrations and the amino acid combination.Additional studies documented that glucose and amino acid responses of both rat and mouse islets were amplified by carbachol or forskolin. However, wortmannin, a phosphatidylinositol 3-kinase inhibitor, amplified only the responses to glucose leaving the responses to the amino acid mixture unaltered. These observations support the concept that mitochondrial metabolism alone is minimally effective in stimulating insulin secretion from islets. The activation of the supplementary second messenger systems (PLC and/or cAMP) appears essential for the emergence of their full secretory potential. The mechanism regulating the potency and specificity of wortmannin's impact on glucose-induced secretion remains to be identified; however a unique mechanism is supported by these findings.

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Time-Dependent Stimulation of Insulin Exocytosis by 3′,5′-Cyclic Adenosine Monophosphate in the Rat Islet β-Cell

Cited by 26 publications

References 48 publications

Glucose-incretin interaction revisited [Review]

Glucose-incretin interaction revisited [Review]

Glucose‐stimulated insulin secretion: A newer perspective

Comparative effects of amino acids and glucose on insulin secretion from isolated rat or mouse islets

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