Elevated glucagon-like peptide-1 plasma levels, as a possible adaptive response, in diabetic NOD mice

Rydgren, Tobias; Börjesson, Andreas; Carlsson, Annika; Sandler, Stellan

doi:10.1016/j.bbrc.2012.06.011

Cited by 10 publications

(11 citation statements)

References 23 publications

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“…Black bars, saline; white bars, glucose MO, USA) concentrations of approximately 30 pmol/l peaked around 15 min after oral stimulation [31], strongly contrasting to the levels obtained by others [32][33][34][35] using sandwich ELISA techniques (which usually measure concentrations around 0 pmol/l), raising doubts as to the validity of this measurement. Others have used sandwich ELISAs (similar to those described here) and have also reported a rapid increase in immunoreactive GLP-1 within the first few minutes [36,37]-similar to the glucagon profile described here. Such rapid increases may be due to cross-reactivity in the sandwich assays [30] with the (inactive) pancreatic isoform GLP-1(1-36)NH 2 , which is co-secreted with glucagon (probably in response to acute stress elicited by the gavage procedure).…”

Section: Discussionsupporting

confidence: 77%

“…Notably, GLP-1(9-36)NH 2 was stable when incubated in assay buffer, suggesting that the observed degradation in plasma was dependent on proteases present in plasma, rather than representing non-specific instability or analytical inadequacies. Theoretically, the C-terminal fragment, GLP-1 (28)(29)(30)(31)(32)(33)(34)(35)(36) amide, should be measurable by C-terminal analysis but not with the sandwich ELISAs; this was demonstrated to be the case, using a synthetic replica of the fragment. Accordingly, the new customised C-terminal ELISA revealed preserved GLP-1 immunoreactivity in the in vitro experiments and secretory profiles of GLP-1 in vivo, which, unlike those obtained with the sandwich ELISAs, correlated to those of glucose absorption (blood glucose), GIP and insulin in a physiologically meaningful manner.…”

Section: Discussionmentioning

confidence: 99%

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Why is it so difficult to measure glucagon-like peptide-1 in a mouse?

et al. 2017

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Why is it so difficult to measure glucagon-like peptide-1 in a mouse?

et al. 2017

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“…Islets from obese, insulin resistant [54] and type 2 diabetic [55] human donors generate GLP-1 whereas control islets from normal human subjects do not [54,55]. Alpha cell hyperplasia is also seen in type 1 autoimmune diabetes in which autoreactive T cells attack and destroy beta cells [56-58]. In the NOD autoimmunity mouse, alpha cell mass is increased.…”

Section: Introductionmentioning

confidence: 99%

“…In the NOD autoimmunity mouse, alpha cell mass is increased. Plasma GLP-1 levels in these mice are increased by 5 to 200-fold [58]. A demonstration of the development of alpha cell hyperplasia in diabetic human subjects in response to diabetes is provided in the report by Butler et al [59].…”

Section: Introductionmentioning

confidence: 99%

Evolving function and potential of pancreatic alpha cells

Stanojević

Habener

2015

Best Practice & Research Clinical Endocrinology & Metab

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The alpha cells that co-occupy the islets in association with beta cells have been long recognized as the source of glucagon, a hyperglycemia-producing and diabetogenic hormone. Although the mechanisms that control the functions of alpha cells, glucagon secretion, and the role of glucagon in diabetes have remained somewhat enigmatic over the fifty years since their discovery, seminal findings during the past few years have moved alpha cells into the spotlight of scientific discovery. These findings obtained largely from studies in mice are: Alpha cells have the capacity to trans-differentiate into insulin-producing beta cells. Alpha cells contain a GLP-1 generating system that produces GLP-1 locally for paracrine actions within the islets that likely promotes beta cell growth and survival and maintains beta cell mass. Impairment of glucagon signaling both prevents the occurrence of diabetes in conditions of the near absence of insulin and expands alpha cell mass. Alpha cells appear to serve as helper cells or guardians of beta cells to ensure their health and well-being. Of potential relevance to the possibility of promoting the transformation of alpha to beta cells is the observation that impairment of glucagon signaling leads to a marked increase in alpha cell mass in the islets. Such alpha cell hyperplasia provides an increased supply of alpha cells for their transdifferentiation into new beta cells. In this review we discuss these recent discoveries from the perspective of their potential relevance to the treatment of diabetes.

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“…GLP‐1 levels were elevated in patients with insulin resistance and diabetes in several studies . Moreover, total plasma GLP‐1 levels are also increased in non‐obese diabetic mice compared with those in normoglycaemic mice . GLP‐1 secretion is impaired in subjects with T2DM .…”

Section: Discussionmentioning

confidence: 99%