The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice

Chambers, Adam P.; Sorrell, Joyce; Haller, April; Roelofs, Karen J.; Hutch, Chelsea R.; Kim, Ki‐Suk; Gutiérrez‐Aguilar, Ruth; Li, Bailing; Drucker, Daniel J.; D’Alessio, David A.; Seeley, Randy J.; Sandoval, Darleen A.

doi:10.1016/j.cmet.2017.02.008

Cell Metabolism

2017

DOI: 10.1016/j.cmet.2017.02.008

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The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice

Adam P. Chambers

¹

,

Joyce Sorrell

²

,

April Haller

³

et al.

Abstract: Summary Glucagon-like peptide 1 (GLP-1) is necessary for normal gluco-regulation, and it has been widely presumed that this function reflects the actions of GLP-1 released from enteroendocrine L-cells. To test the relative importance of intestinal vs. pancreatic sources of GLP-1 for physiological regulation of glucose, we administered a GLP-1R antagonist, exendin 9–39 (Ex9), to mice with tissue-specific reactivation of the preproglucagon gene (Gcg). Ex9 impaired glucose tolerance in wild-type mice but had no i… Show more

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Cited by 210 publications

(235 citation statements)

References 30 publications

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“…To validate these findings in the inducible model, Ex9, or saline (Sal) was injected 15 minutes before a glucose gavage ( Figure 1, C and D). Similar to our previous finding (18), glucose levels were significantly higher after Ex9 in control VilCreERT2 mice but had no effect on glucose levels in the GcgRA ΔVilCreERT2 mice. These data indicate intestinally secreted GLP-1 does not regulate glucose tolerance in mice under these conditions and replicates our previous data.…”

Section: Resultssupporting

confidence: 91%

Glycemic effect of pancreatic preproglucagon in mouse sleeve gastrectomy

Kim

¹

,

Hutch

²

,

Wood

³

et al. 2019

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…To validate these findings in the inducible model, Ex9, or saline (Sal) was injected 15 minutes before a glucose gavage ( Figure 1, C and D). Similar to our previous finding (18), glucose levels were significantly higher after Ex9 in control VilCreERT2 mice but had no effect on glucose levels in the GcgRA ΔVilCreERT2 mice. These data indicate intestinally secreted GLP-1 does not regulate glucose tolerance in mice under these conditions and replicates our previous data.…”

Section: Resultssupporting

confidence: 91%

Glycemic effect of pancreatic preproglucagon in mouse sleeve gastrectomy

Kim

¹

,

Hutch

²

,

Wood

³

et al. 2019

Self Cite

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…Ex9 and linagliptin administered together to VilCre control mice but not GcgRA ΔVilCre or GcgRA ΔNull mice produced elevated basal glucose (−15 min) and all mice had a significantly lower glucose excursion compared with Ex9 treatment alone at 15-60 min after the glucose load. These findings are consistent with our previous findings [9] but do not fit with the conventional model, whereby GLP-1 secreted into the circulation from the gut mediates the effects of DPP-4 inhibitor action [13].…”

Section: Resultssupporting

confidence: 89%

The role of GIP and pancreatic GLP-1 in the glucoregulatory effect of DPP-4 inhibition in mice

Hutch

¹

,

Roelofs

²

,

Haller

³

et al. 2019

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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“…It is curious if this phenomenon is present in islet β-cells in vivo. Consistent with our data, recent studies showed that intraislet GLP-1 and/or glucagon are essential for maintaining proper β-cell responsiveness to glucose and regulating glucose homeostasis 37 – 41 . Glucagon was shown to bind to GLP-1 receptors and elevate cAMP levels of β-cells.…”

Section: Discussionsupporting

confidence: 93%

Establishment of a long-term stable β-cell line and its application to analyze the effect of Gcg expression on insulin secretion

Miyazaki

¹

,

Tashiro

²

,

Tsuchiya

³

et al. 2021

Sci Rep

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

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