ATP-sensitive potassium channel (KATPchannel) expression in the normal canine pancreas and in canine insulinomas

Donley, V.; Hiskett, Erin K; Kidder, Aimee C.; Schermerhorn, Thomas

doi:10.1186/1746-6148-1-8

Cited by 11 publications

(4 citation statements)

References 24 publications

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“…Proton leak activity of UCP2 has an important role in negative regulation of insulin secretion via its inhibition of ATP synthesis in b-cells (Jezek 2002). Pancreatic endocrine b-cells are glucose-sensing cells equipped with a K ATP channel consisting of two subunits, SUR1 and Kir6.2 (Donley et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Uncoupling protein 2 negatively regulates glucose-induced glucagon-like peptide 1 secretion

Zhang

Li²,

Liang³

et al. 2012

Journal of Molecular Endocrinology

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It is known that endogenous levels of the incretin hormone glucagon-like peptide 1 (GLP1) can be enhanced by various secretagogues, but the mechanism underlying GLP1 secretion is still not fully understood. We assessed the possible effect of uncoupling protein 2 (UCP2) on GLP1 secretion in mouse intestinal tract and NCI-H716 cells, a wellcharacterized human enteroendocrine L cell model. Localization of UCP2 and GLP1 in the gastrointestinal tract was assessed by immunofluorescence staining. Ucp2 mRNA levels in gut were analyzed by quantitative RT-PCR. Human NCI-H716 cells were transiently transfected with siRNAs targeting UCP2. The plasma and ileum tissue levels of GLP1 (7-36) amide were measured using an ELISA kit. UCP2 was primarily expressed in the mucosal layer and colocalized with GLP1 in gastrointestinal mucosa. L cells secreting GLP1 also expressed UCP2. After glucose administration, UCP2-deficient mice showed increased glucose-induced GLP1 secretion compared with wild-type littermates. GLP1 secretion increased after NCI-H716 cells were transfected with siRNAs targeting UCP2. UCP2 was markedly upregulated in ileum tissue from ob/ob mice, and GLP1 secretion decreased compared with normal mice. Furthermore, GLP1 secretion increased after administration of genipin by oral gavage. Taken together, these results reveal an inhibitory role of UCP2 in glucose-induced GLP1 secretion.

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Section: Introductionmentioning

confidence: 99%

Uncoupling protein 2 negatively regulates glucose-induced glucagon-like peptide 1 secretion

Zhang

Li²,

Liang³

et al. 2012

Journal of Molecular Endocrinology

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“…6 The relationship between GCK and HK1 gene expression in insulinoma has not been reported previously in any species, and information about expression of other genes involved in glucose metabolism by insulinomas is scant. [13][14][15] We found that the insulinoma overexpressed GCK compared with normal pancreatic tissue from the same cat, but HK1 expression was nearly equivalent in both tissues. Comparison of GCK expression in tumor and feline islets might have provided additional information.…”

Section: Discussionmentioning

confidence: 99%

Cellular and Molecular Characterization of a Feline Insulinoma

Jackson

DeBey

Lindbloom-Hawley

et al. 2009

Veterinary Internal Medicne

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Background: Insulinoma is an autonomous insulin-secreting islet cell neoplasm that is rarely diagnosed in cats. The clinical and pathological aspects of feline insulinoma have been described previously, but the molecular characteristics of these tumors have not been investigated.Objectives: The study objectives were to characterize peptide hormone production and determine expression of selected genes involved in glucose metabolism and insulin secretion in a feline insulinoma.Methods: Immunohistochemistry and RT-PCR were used to examine hormone and gene expression, respectively, by insulinoma cells.Results: Immunohistochemistry examination indicated that the tumor cells expressed insulin, chromogranin A, and somatostatin but not glucagon or pancreatic polypeptide. The tumor expressed several genes characteristic of pancreatic beta cells (b cells) including insulin (INS), glucose transporter 2 (GLUT2), and glucokinase (GCK). The tumor also expressed hexokinase 1 (HK1), a glycolytic enzyme not normally expressed in b cells. GCK expression was higher in the insulinoma than in normal pancreas from the same cat. The GCK : HK1 ratio was 420-fold higher in insulinoma tissue than in normal pancreas.Conclusions and Clinical Importance: The feline insulinoma produced several peptide hormones and expressed genes consistent with a b-cell phenotype. The pattern of hexokinase gene expression in tumor cells differed from that of normal pancreas. These findings suggest insulinoma cells may have an increased sensitivity to glucose that could contribute to the abnormal insulin secretory response observed at low serum glucose concentrations.

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“…Potassium channels play an important role in regulating insulin secretion from the beta cells of the pancreas. Pancreatic beta cells express ATP-sensitive potassium (KATP) channels that are needed for normal insulin secretion and are targets for drugs that modulate insulin secretion [ 37 ]. When glucose levels are high, glucose enters the beta cells and triggers a series of events that lead to the opening of potassium channels.…”

Section: Antidiabetic Medicationsmentioning

confidence: 99%

Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control

Youssef

Yahya

Popoviciu

et al. 2023

IJMS

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The number of diabetic patients has risen dramatically in recent decades, owing mostly to the rising incidence of type 2 diabetes mellitus (T2DM). Several oral antidiabetic medications are used for the treatment of T2DM including, α-glucosidases inhibitors, biguanides, sulfonylureas, meglitinides, GLP-1 receptor agonists, PPAR-γ agonists, DDP4 inhibitors, and SGLT2 inhibitors. In this review we focus on the possible effects of SGLT2 inhibitors on different body systems. Beyond the diabetic state, SGLT2 inhibitors have revealed a demonstrable ability to ameliorate cardiac remodeling, enhance myocardial function, and lower heart failure mortality. Additionally, SGLT2 inhibitors can modify adipocytes and their production of cytokines, such as adipokines and adiponectin, which enhances insulin sensitivity and delays diabetes onset. On the other hand, SGLT2 inhibitors have been linked to decreased total hip bone mineral deposition and increased hip bone resorption in T2DM patients. More data are needed to evaluate the role of SGLT2 inhibitors on cancer. Finally, the effects of SGLT2 inhibitors on neuroprotection appear to be both direct and indirect, according to scientific investigations utilizing various experimental models. SGLT2 inhibitors improve vascular tone, elasticity, and contractility by reducing oxidative stress, inflammation, insulin signaling pathways, and endothelial cell proliferation. They also improve brain function, synaptic plasticity, acetylcholinesterase activity, and reduce amyloid plaque formation, as well as regulation of the mTOR pathway in the brain, which reduces brain damage and cognitive decline.

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ATP-sensitive potassium channel (KATPchannel) expression in the normal canine pancreas and in canine insulinomas

Cited by 11 publications

References 24 publications

Uncoupling protein 2 negatively regulates glucose-induced glucagon-like peptide 1 secretion

Uncoupling protein 2 negatively regulates glucose-induced glucagon-like peptide 1 secretion

Cellular and Molecular Characterization of a Feline Insulinoma

Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control

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