The intravenous glucose tolerance test in cannulated Wistar rats: A robust method for the in vivo assessment of glucose-stimulated insulin secretion

Frangioudakis, Georgia; Gyte, Amy; Loxham, Susan J. G.; Poucher, Simon M.

doi:10.1016/j.vascn.2007.12.002

Cited by 30 publications

(16 citation statements)

References 22 publications

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“…The rapid increase in serum insulin levels observed in this figure confirms, in this model, the classical profile of glucose-stimulated insulin secretion and these results are according to that reported by Frangioudakis et al (2008)[27].…”

supporting

confidence: 93%

Antihyperglycemic activity of naphthylchalcones

Damazio

Zanatta

Cazarolli

et al. 2010

European Journal of Medicinal Chemistry

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supporting

confidence: 93%

Antihyperglycemic activity of naphthylchalcones

Damazio

Zanatta

Cazarolli

et al. 2010

European Journal of Medicinal Chemistry

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“…Parkes et al (30) reported that iv Ex-4 caused a dose-dependent increase of insulin in anesthetized Lewis rats, without a significant effect on iv glucose tolerance, although both the treated and control animals in this experiment were relatively hyperglycemic with fasting values Ͼ10 mM. Similarly, Fran- gioudakis et al (12) demonstrated that iv Ex-4 enhanced glucose-stimulated insulin secretion in anesthetized and conscious Wistar rats without significant differences in blood glucose compared with controls. These studies used Ex-4 doses of Յ10 g/kg, comparable with those used in our experiments.…”

Section: Discussionmentioning

confidence: 59%

Exendin-4 increases blood glucose levels acutely in rats by activation of the sympathetic nervous system

Pérez-Tilve

González-Matías

Aulinger

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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, an agonist of the glucagon-like peptide-1 receptor (GLP-1R), shares many of the actions of GLP-1 on pancreatic islets, the central nervous system (CNS), and the gastrointestinal tract that mediates glucose homeostasis and food intake. Because Ex-4 has a much longer plasma half-life than GLP-1, it is an effective drug for reducing blood glucose levels in patients with type 2 diabetes mellitus (T2DM). Here, we report that acute administration of Ex-4, in relatively high doses, into either the peripheral circulation or the CNS, paradoxically increased blood glucose levels in rats. This effect was independent of the insulinotropic and hypothalamic-pituitary-adrenal activating actions of Ex-4 and could be blocked by a GLP-1R antagonist. Comparable doses of GLP-1 did not induce hyperglycemia, even when protected from rapid metabolism by a dipeptidyl peptidase IV inhibitor. Acute hyperglycemia induced by Ex-4 was blocked by hexamethonium, guanethidine, and adrenal medullectomy, indicating that this effect was mediated by sympathetic nervous system (SNS) activation. The potency of Ex-4 to elevate blood glucose waned with chronic administration such that after 6 days the familiar actions of Ex-4 to improve glucose tolerance were evident. These findings indicate that, in rats, high doses of Ex-4 activate a SNS response that can overcome the expected benefits of this peptide on glucose metabolism and actually raise blood glucose. These results have important implications for the design and interpretation of studies using Ex-4 in rats. Moreover, since there are many similarities in the response of the GLP-1R system across mammalian species, it is important to consider whether there is acute activation of the SNS by Ex-4 in humans.glucagon-like peptide-1; glycemia

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“…IVIRT was performed to detect islet function as previously reported [7] . Blood (1 mL) was sampled 0 (before glucose injection), 2, 5, 10, 30 min after glucose injection for the radioimmunoassay of plasma insulin.…”

Section: Methods Of Detection 131 Intravenous Insulin Release Test mentioning

confidence: 99%

Effect of renin angiotensin system blockade on the islet microvessel density of diabetic rats and its relationship with islet function

et al. 2009

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin (30 mg/kg). After 8 weeks intervention with perindopril (AE, n=10) or valsartan (AR, n=10), the islet function of the animals was evaluated by intravenous insulin release test (IVIRT). The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor (VEGF) in the islets. The microvessel density (MVD) of islets was detected by counting CD34 positive cells. The hypoxia inducible factor (HIF)-1alpha mRNA expression in the islets was detected by RT-PCR. Compared with normal control group (NC, n=10), the area under the curve for insulin from 0 to 30 min (AUCI(0-30)) of diabetes group (DM, n=8) was decreased by 66.3%; the insulin relative concentration (IRC) of betacell was decreased significantly; the relative content of VEGF was increased obviously [(-4.21+/-0.13) vs (-4.06+/-0.29)]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1alpha mRNA was increased by 1.19 times (all P<0.01). Compared with DM group, the AUCI(0-30) of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1alpha was decreased by 27.2% and 29.0% respectively (all P<0.01 or P<0.05). There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.

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The intravenous glucose tolerance test in cannulated Wistar rats: A robust method for the in vivo assessment of glucose-stimulated insulin secretion

Cited by 30 publications

References 22 publications

Antihyperglycemic activity of naphthylchalcones

Antihyperglycemic activity of naphthylchalcones

Exendin-4 increases blood glucose levels acutely in rats by activation of the sympathetic nervous system

Effect of renin angiotensin system blockade on the islet microvessel density of diabetic rats and its relationship with islet function

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