Islet adaptation in GIP receptor knockout mice

• Glucose-dependent insulinotropic polypeptide (GIP) receptor knockout (KO) mice are tools for studying GIP physiology. Previous results have demonstrated that these mice have impaired insulin response to oral glucose. In this study, we examined the insulin response to intravenous glucose by measuring glucose, insulin and C-peptide after intravenous glucose (0.35 g/kg) in 5-h fasted female GIP receptor KO mice and their wild-type (WT) littermates. The 1 min insulin and C-peptide responses to intravenous glucose were significantly enhanced in GIP receptor KO mice (n = 26) compared to WT mice (n = 30) as was beta cell function (area under the 50 min C-peptide curve divided by area under the 50 min curve for glucose) (P = 0.001). Beta cell function after intravenous glucose was also enhanced in GIP receptor KO mice in the presence of the glucagon-like peptide-1 receptor antagonist exendin 9 (30 nmol/kg; P = 0.007), the muscarinic antagonist atropine (5 mg/kg; P = 0.007) and the combination of the alpha-adrenoceptor antagonist yohimbine (1.4 mg/kg) and the beta-adrenoceptor antagonist propranolol (2.5 mg/kg; P = 0.042). Analysis of the regression between fasting glucose (6.8 ± 0.1 mmol/l in GIP receptor KO mice and 7.5 ± 0.2 mmol/l in WT mice, P = 0.003) and the 1 min C-peptide response to intravenous glucose showed a negative linear regression between these variables in both WT (n = 60; r = −0.425, P = 0.001) and GIP receptor KO mice (n = 56; r = −0.474, P < 0.001). We conclude that there is a beta cell adaptation in GIP receptor KO mice resulting in enhanced insulin secretion after intravenous glucose to which slight long-term reduction in circulating glucose in these mice may contribute.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Adrenergic

Beta cell function

C-peptide

Cholinergic

GIP

GLP-1

Insulin

Knockout mice

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