Glucagonlike peptide-1 (7–36)amide suppresses glucagon secretion and decreases cyclic AMP concentration in cultured in-R1-G9 cells

Matsumura, Toshiko; Itoh, H.; Watanabe, Nobuaki; Oda, Yasuo; Tanaka, Misuzu; Namba, Mitsuyoshi; Kôno, Norio; Matsuyama, Tatsuo; Komatsu, Ryoya; Matsuzawa, Yūji

doi:10.1016/s0006-291x(05)80836-8

Cited by 19 publications

(7 citation statements)

References 10 publications

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“…The glucagonostatic effect of GLP-1 does not appear to be mediated by a local endocrine effect of insulin, since glucagon release is inhibited even when insulin is unstimulated [61,64]. This is supported by the observation that GLP-1 also inhibits glucagon release from a glucagon-secreting cell line [66].…”

Section: Effects Of Glp-1 On Alpha Cells In Vitromentioning

confidence: 81%

Alpha cell function in health and disease: influence of glucagon-like peptide-1

Dunning¹,

2005

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Although there is abundant evidence that hyperglucagonaemia plays a key role in the development of hyperglycaemia in type 2 diabetes, efforts to understand and correct this abnormality have been overshadowed by the emphasis on insulin secretion and action. However, recognition that the incretin hormone glucagon-like peptide-1 (GLP-1) exerts opposing effects on glucagon and insulin secretion has revived interest in glucagon, the neglected partner of insulin, in the bihormonal hypothesis. In healthy subjects, glucagon secretion is regulated by a variety of nutrient, neural and hormonal factors, the most important of which is glucose. The defect in alpha cell function that occurs in type 2 diabetes reflects impaired glucose sensing. GLP-1 inhibits glucagon secretion in vitro and in vivo in experimental animals, and suppresses glucagon release in a glucose-dependent manner in healthy subjects. This effect is also evident in diabetic patients, but GLP-1 does not inhibit glucagon release in response to hypoglycaemia, and may even enhance it. Early clinical studies with agents acting through GLP-1 signalling mechanisms (e.g. exenatide, liraglutide and vildagliptin) suggest that GLP-1 can improve alpha cell glucose sensing in patients with type 2 diabetes. Therapeutic approaches based around GLP-1 have the potential to improve both alpha cell and beta cell function, and could be of benefit in patients with a broad range of metabolic disorders.

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Section: Effects Of Glp-1 On Alpha Cells In Vitromentioning

confidence: 81%

Alpha cell function in health and disease: influence of glucagon-like peptide-1

Dunning¹,

2005

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“…It has been acknowledged that GLP-1 suppresses glucagon release (30). Such suppression is independent of the increased insulin secretion in that it occurs even in cultured islet α cell lines (31). Furthermore, it has been reported that GLP-1 treatment stimulates islet β cells without obvious changes in other cell types (32).…”

Section: Discussionmentioning

confidence: 99%

Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes

Hao

Zhang

et al. 2017

International Journal of Molecular Medicine

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Long-term exposure to a high-fat diet (HFD) causes glucotoxicity and lipotoxicity in islet β cells and leads to the development of metabolic dysfunctions. Reductions in pancreatic and duodenal homeobox-1 (PDX-1) expression have been shown to induce type 2 diabetes mellitus by causing impairments to islet β cells. Glucagon-like peptide 1 (GLP-1) treatment reduces endogenous insulin resistance in HFD-induced type 2 diabetes mellitus. In the present study, the underlying mechanism by which GLP-1 exerts its function in type 2 diabetes mellitus was investigated. The effect of liraglutide (GLP-1 receptor agonist) administration on glucose tolerance, insulin release, and glucose-dependent insulinotropic polypeptide level was detected in a HFD-induced diabetes C57/BL6 mouse model. Moreover, the role of liraglutide administration on the activity of PDX-1 was quantified to demonstrate the association between the two indicators. The results showed that administration of liraglutide could ameliorate the impairments to β cells due to HFD consumption. Liraglutide restored the insulin capacity and stimulated glucose disposal by improving the function and increasing the number of islet β cells. Furthermore, the hyperplasia and redundant function of islet α cells were inhibited by liraglutide treatment as well. At the molecular level, administration of liraglutide induced the expression of PDX-1, MafA, p-JAK2 and p-Stat3 in HFD model to relatively normal levels. It was suggested that the effect of liraglutide-induced activation of GLP-1 was exerted via activation of PDX-1 rather than its function in decreasing body weight. The study demonstrated that GLP-1 played an essential role in type 2 diabetes mellitus.

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“…The wild-type INR1-G9 cells do not contain transcripts for GLP-1R (Dillon et al, 2005;Fig 5). Matsumura and colleagues (Matsumura et al, 1992) have shown that GLP-1 decreased cAMP and suppressed glucagon secretion in INR1-G9 cells. However, given that we and the Dillon laboratory do not observe the expression of GLP-1R in this cell line, the mechanism for this is difficult to comprehend.…”

Section: Effects On Glucagon Secretion Are They Direct or Indirect?mentioning

confidence: 96%

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

Doyle

Egan

2007

Pharmacology & Therapeutics

577

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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Glucagonlike peptide-1 (7–36)amide suppresses glucagon secretion and decreases cyclic AMP concentration in cultured in-R1-G9 cells

Cited by 19 publications

References 10 publications

Alpha cell function in health and disease: influence of glucagon-like peptide-1

Alpha cell function in health and disease: influence of glucagon-like peptide-1

Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes

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

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