GLP-1 action in L6 myotubes is via a receptor different  from the pancreatic GLP-1 receptor

Yang, Huan; Egan, Josephine M.; Wang, Y.; Cd, Moyes; Roth, Jesse; Montrose, Marshall H.; Montrose‐Rafizadeh, Chahrzad

doi:10.1152/ajpcell.1998.275.3.c675

Cited by 129 publications

(66 citation statements)

References 24 publications

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“…4B), whereas the control animals showed their first sign of peripheral insulin responsiveness (46%) only during the latter infusion step. These data suggest a marked left shift in insulin-stimulated peripheral glucose uptake and are consistent with our previous demonstration of increased glucose uptake in soleus muscle (21) and with several reports of incretin-stimulated increases in glucose uptake (30,39). A number of studies using GLP-1 receptor agonists over the long term have suggested similar improvements in insulin sensitivity (38).…”

Section: Discussionsupporting

confidence: 92%

“…Since the early 1990s, numerous studies have revealed a pleiotropy of antidiabetic effects triggered by interaction of the incretins with their respective cell-surface receptors. Among them are stimulation of ␤-cell glucose competence, proliferation, differentiation, growth, and cell survival; inhibition of glucagon secretion; and several reports indicating stimulation of glucose uptake in muscle cells (2)(3)(4)(5)(6)(7)30,31). Recently, we showed that long-term DP IV inhibitor therapy caused marked improvements in glucose tolerance, hyperinsulinemia, and ␤-cell function in the VDF rat, findings that highlight the potential utility of these compounds in diabetes therapy.…”

Section: Discussionmentioning

confidence: 84%

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Long-Term Treatment With Dipeptidyl Peptidase IV Inhibitor Improves Hepatic and Peripheral Insulin Sensitivity in the VDF Zucker Rat

et al. 2002

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Upon release into circulation, the potent insulin secretagogues glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are rapidly cleaved and inactivated by the enzyme dipeptidyl peptidase IV (DP IV). Long-term administration of specific DP IV inhibitors, so as to enhance circulating active GIP and GLP-1 levels, has been shown to improve glucose tolerance and ␤-cell glucose responsiveness and to reduce hyperinsulinemia in the Vancouver diabetic fatty (VDF) rat model of type 2 diabetes. Using the VDF model, the current study was undertaken to examine the effects of long-term DP IV inhibitor treatment on insulin sensitivity. Euglycemic-hyperinsulinemic clamps were performed on two sets of conscious VDF rats treated with or without the DP IV inhibitor P32/98 (20 mg ⅐ kg -1 ⅐ day -1 for 12 weeks). The protocol consisted of three sequential 90-min periods with insulin infusion rates of 0, 5, and 15 mU ⅐ kg -1 ⅐ min -1 and included a constant infusion of [ 3 H]glucose for measure of hepatic and peripheral insulin sensitivity. Relative to untreated littermates, the treated animals showed a left shift in the sensitivity of hepatic glucose output to insulin (average reduction ϳ6 mol ⅐ kg -1 ⅐ min -1 ) and a marked gain in peripheral responsiveness to insulin, with glucose disposal rates increasing 105 and 216% in response to the two insulin steps (versus 2 and 46% in controls). These results provide the first demonstration of improved hepatic and peripheral insulin sensitivity after DP IV inhibitor therapy, and coupled with apparent improvements in ␤-cell function, they offer strong support for the utility of these compounds in the treatment of diabetes.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 84%

Long-Term Treatment With Dipeptidyl Peptidase IV Inhibitor Improves Hepatic and Peripheral Insulin Sensitivity in the VDF Zucker Rat

et al. 2002

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“…The specific activity of the eluted HMGB1 was 2.8 ϫ 10 6 cpm͞g of protein. The cell surface binding of HMGB1 or A box to macrophage cultures was performed according to a described protocol (19). In brief, RAW 264.7 cells were plated in 24-well plates and grown to confluence.…”

Section: Methodsmentioning

confidence: 99%

Reversing established sepsis with antagonists of endogenous high-mobility group box 1

Yang

Ochani

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

1,034

974

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Despite significant advances in intensive care therapy and antibiotics, severe sepsis accounts for 9% of all deaths in the United States annually. The pathological sequelae of sepsis are characterized by a systemic inflammatory response, but experimental therapeutics that target specific early inflammatory mediators [tumor necrosis factor (TNF) and IL-1␤] have not proven efficacious in the clinic. We recently identified high mobility group box 1 (HMGB1) as a late mediator of endotoxin-induced lethality that exhibits significantly delayed kinetics relative to TNF and IL-1␤. Here, we report that serum HMGB1 levels are increased significantly in a standardized model of murine sepsis, beginning 18 h after surgical induction of peritonitis. Specific inhibition of HMGB1 activity [with either anti-HMGB1 antibody (600 g per mouse) or the DNAbinding A box (600 g per mouse)] beginning as late as 24 h after surgical induction of peritonitis significantly increased survival (nonimmune IgG-treated controls ‫؍‬ 28% vs. anti-HMGB1 antibody group ‫؍‬ 72%, P < 0.03; GST control protein ‫؍‬ 28% vs. A box ‫؍‬ 68%, P < 0.03). Animals treated with either HMGB1 antagonist were protected against the development of organ injury, as evidenced by improved levels of serum creatinine and blood urea nitrogen. These observations demonstrate that specific inhibition of endogenous HMGB1 therapeutically reverses lethality of established sepsis indicating that HMGB1 inhibitors can be administered in a clinically relevant time frame.

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“…On this basis, Ex9-39 is considered to be an inverse agonist of the GLP-1 receptor (26). In contrast, in some studies Ex9-39 does not antagonize GLP-1 action or may even behave as an agonist (27)(28)(29)(30). These observations raise the possibility that although Ex9-39 effectively antagonized the incretin effect of endogenous GLP-1, the growth-promoting effect was not antagonized.…”

Section: Glp-1 In Pancreatic Regenerationmentioning

confidence: 99%

Role of Endogenous Glucagon-Like Peptide-1 in Islet Regeneration After Partial Pancreatectomy

et al. 2003

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A reduction in ␤-cell mass is an important causative factor in type 1 and type 2 diabetes. Glucagon-like peptide-1 (GLP-1) and the long-acting agonist exendin 4 (Ex-4) expand ␤-cell mass by stimulating neogenesis and proliferation. In the partial pancreatectomy (Ppx) model, exogenous Ex-4 promotes islet regeneration, leading to sustained improvement in glucose tolerance. In this study, we investigate the potential role of endogenous GLP-1 in islet growth. We examined ␤-cell mass regeneration after 70% Ppx in mice receiving the GLP-1 antagonist Ex9-39 and in GLP-1R ؊/؊ mice. In Ex9-39 -treated sham-operated mice, persistent fasting hyperglycemia was observed, but ␤-cell mass was not diminished. In pancreatectomized mice, persistent glucose intolerance was noted, but this was not further exacerbated by Ex9-39. Accordingly, ␤-cell mass recovery of Ppx mice was not impaired by Ex9-39. In contrast, GLP-1R؊/؊ CD1 mice showed worse glucose intolerance after Ppx compared with wild-type CD1 Ppx mice, and this correlated with a significant defect in ␤-cell mass regeneration. The recovery of ␤-cell mass differed markedly in the BALB/c and CD1 control mice, indicating a significant role of genetic background in the regulation of ␤-cell mass. These studies point to a role for endogenous GLP-1 in ␤-cell regeneration after Ppx in mice.

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GLP-1 action in L6 myotubes is via a receptor different from the pancreatic GLP-1 receptor

Cited by 129 publications

References 24 publications

Long-Term Treatment With Dipeptidyl Peptidase IV Inhibitor Improves Hepatic and Peripheral Insulin Sensitivity in the VDF Zucker Rat

Long-Term Treatment With Dipeptidyl Peptidase IV Inhibitor Improves Hepatic and Peripheral Insulin Sensitivity in the VDF Zucker Rat

Reversing established sepsis with antagonists of endogenous high-mobility group box 1

Role of Endogenous Glucagon-Like Peptide-1 in Islet Regeneration After Partial Pancreatectomy

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