Distinct Effects of Glucose-Dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 on Insulin Secretion and Gut Motility

Miki, Takashi; Minami, Kohtaro; Shinozaki, Hirotsugu; Matsumura, K.; Saraya, Atsunori; Ikeda, Hiroki; Yamada, Yoshio; Holst, Jens J.; Seino, Susumu

doi:10.2337/diabetes.54.4.1056

Cited by 109 publications

(106 citation statements)

References 47 publications

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“…mice at 15 min after glucose loading were significantly higher than those in Kir6.2 C/C mice (PZ0.021) (Fig. 3a), and are consistent with results described in a previous report (Miki et al 2005). Plasma GIP levels at 15 min with voluntary feeding on dextrin were higher than those with voluntary feeding on standard chow in both Kir6.2 C/C mice and Kir6.2 K/K mice, indicating that carbohydrate is a powerful GIP secretagogue.…”

Section: Metabolism Of Glucose In K-cells Is Not Essential For Gip Sesupporting

confidence: 82%

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KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state

Ogata¹,

Seino²,

Harada³

et al. 2014

Journal of Endocrinology

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Glucose-dependent insulinotropic polypeptide (GIP), a gut hormone secreted from intestinal K-cells, potentiates insulin secretion. Both K-cells and pancreatic b-cells are glucoseresponsive and equipped with a similar glucose-sensing apparatus that includes glucokinase and an ATP-sensitive K C (K ATP ) channel comprising KIR6.2 and sulfonylurea receptor 1. In absorptive epithelial cells and enteroendocrine cells, sodium glucose co-transporter 1 (SGLT1) is also known to play an important role in glucose absorption and glucose-induced incretin secretion. However, the glucose-sensing mechanism in K-cells is not fully understood. In this study, we examined the involvement of SGLT1 (SLC5A1) and the K ATP channels in glucose sensing in GIP secretion in both normal and streptozotocin-induced diabetic mice. Glimepiride, a sulfonylurea, did not induce GIP secretion and pretreatment with diazoxide, a K ATP channel activator, did not affect glucose-induced GIP secretion in the normal state. In mice lacking K ATP channels (Kir6.2 K/K mice), glucose-induced GIP secretion was enhanced compared with control (Kir6.2 C/C ) mice, but was completely blocked by the SGLT1 inhibitor phlorizin. In Kir6.2 K/K mice, intestinal glucose absorption through SGLT1 was enhanced compared with that in Kir6.2 C/C mice. On the other hand, glucose-induced GIP secretion was enhanced in the diabetic state in Kir6.2 C/C mice. This GIP secretion was partially blocked by phlorizin, but was completely blocked by pretreatment with diazoxide in addition to phlorizin administration. These results demonstrate that glucose-induced GIP secretion depends primarily on SGLT1 in the normal state, whereas the K ATP channel as well as SGLT1 is involved in GIP secretion in the diabetic state in vivo.

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Section: Metabolism Of Glucose In K-cells Is Not Essential For Gip Sesupporting

confidence: 82%

“…In contrast to GIIS, GIP secretion in response to oral glucose loading in Kir6.2 K/K mice is somewhat enhanced, compared with that in Kir6.2 C/C mice (Miki et al 2005). This indicates that the K ATP channels in K-cells are activated and involved in the suppression of glucose-induced GIP secretion in the physiological state.…”

Section: Introductionmentioning

confidence: 57%

KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state

Ogata¹,

Seino²,

Harada³

et al. 2014

Journal of Endocrinology

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“…ATP binds to the cytoplasmic side of K ir6.2 subunit in an Mg 2+ -dependent manner initiating a conformational change that results in closure of the channel (Gribble et al, 1998). Depolarization and deactivation of the K ATP channels are entirely responsible for the first phase of insulin secretion as illustrated by the K ATP knockout mice (Miki et al, 2005) and separately by the SUR1 knockout mice (Miki et al, 2005;Shiota et al, 2002). In humans, mutations in either K ir6.2 or K ATP result in a severe form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI; Glaser et al, 1994).…”

Section: Potassium Channelsmentioning

confidence: 99%

“…In humans, mutations in either K ir6.2 or K ATP result in a severe form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI; Glaser et al, 1994). By contrast, absence of K ATP channels in mice results in less severe symptoms where the mice are normoglycemic, displaying glucose intolerance only upon feeding or glucose challenge (Miki et al, 2005;Shiota et al, 2002).…”

Section: Potassium Channelsmentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

583

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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“…We previously generated mice lacking Kir6.2, the pore subunit of the b-cell K ATP channel (Kir6.2 K/K ) (Miki et al 1998), and found that Kir6.2 K/K mice elicit no significant increase in insulin secretion in response to glucose using perifusion of isolated pancreatic islets (Miki et al 1998) and perfusion of pancreas (Miki et al 2005), both of which were performed under denervated, in vitro condition. In Sur1 K/K mice, which lack the regulatory subunit of the channel, only a very small amount of insulin in response to glucose is triggered, as assessed by perfusion of pancreas (Shiota et al 2002) and batch incubation of isolated pancreatic islets (Doliba et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Cephalic phase insulin secretion is KATP channel independent

Seino

Miki

Fujimoto

et al. 2013

Journal of Endocrinology

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Glucose-induced insulin secretion from pancreatic b-cells critically depends on the activity of ATP-sensitive K C channels (K ATP channel). We previously generated mice lacking Kir6.2, the pore subunit of the b-cell K ATP channel (Kir6.2 K/K ), that show almost no insulin secretion in response to glucose in vitro. In this study, we compared insulin secretion by voluntary feeding (self-motivated, oral nutrient ingestion) and by forced feeding (intra-gastric nutrient injection via gavage) in wild-type (Kir6.2 C/C ) and Kir6.2 K/K mice. Under ad libitum feeding or during voluntary feeding of standard chow, blood glucose levels and plasma insulin levels were similar in Kir6.2 C/C and Kir6.2 K/K mice. By voluntary feeding of carbohydrate alone, insulin secretion was induced significantly in Kir6.2 K/K mice but was markedly attenuated compared with that in Kir6.2 C/C mice. On forced feeding of standard chow or carbohydrate alone, the insulin secretory response was markedly impaired or completely absent in Kir6.2 K/K mice. Pretreatment with a muscarine receptor antagonist, atropine methyl nitrate, which does not cross the blood-brain barrier, almost completely blocked insulin secretion induced by voluntary feeding of standard chow or carbohydrate in Kir6.2 K/K mice. Substantial glucose-induced insulin secretion was induced in the pancreas perfusion study of Kir6.2 K/K mice only in the presence of carbamylcholine. These results suggest that a K ATP channel-independent mechanism mediated by the vagal nerve plays a critical role in insulin secretion in response to nutrients in vivo.

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Distinct Effects of Glucose-Dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 on Insulin Secretion and Gut Motility

Cited by 109 publications

References 47 publications

KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state

KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Cephalic phase insulin secretion is KATP channel independent

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