scholarly journals Impaired Hippocampal Glutamate and Glutamine Metabolism in the db/db Mouse Model of Type 2 Diabetes Mellitus

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jens Velde Andersen ◽  
Jakob Dahl Nissen ◽  
Sofie Kjellerup Christensen ◽  
Kia Hjulmand Markussen ◽  
Helle Sønderby Waagepetersen
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Oxygen Consumption ◽  
Mouse Model ◽  
Cerebral Metabolism ◽  
Hippocampal Slices ◽  
Glutamine Metabolism ◽  
Mitochondrial Oxidation

Type 2 diabetes mellitus (T2DM) is a risk factor for the development of Alzheimer’s disease, and changes in brain energy metabolism have been suggested as a causative mechanism. The aim of this study was to investigate the cerebral metabolism of the important amino acids glutamate and glutamine in the db/db mouse model of T2DM. Glutamate and glutamine are both substrates for mitochondrial oxidation, and oxygen consumption was assessed in isolated brain mitochondria by Seahorse XFe96 analysis. In addition, acutely isolated cerebral cortical and hippocampal slices were incubated with [U-13C]glutamate and [U-13C]glutamine, and tissue extracts were analyzed by gas chromatography-mass spectrometry. The oxygen consumption rate using glutamate and glutamine as substrates was not different in isolated cerebral mitochondria of db/db mice compared to controls. Hippocampal slices of db/db mice exhibited significantly reduced 13C labeling in glutamate, glutamine, GABA, citrate, and aspartate from metabolism of [U-13C]glutamate. Additionally, reduced 13C labeling were observed in GABA, citrate, and aspartate from [U-13C]glutamine metabolism in hippocampal slices of db/db mice when compared to controls. None of these changes were observed in cerebral cortical slices. The results suggest specific hippocampal impairments in glutamate and glutamine metabolism, without affecting mitochondrial oxidation of these substrates, in the db/db mouse.

Co-Purification of Recombinant Modified Glucagon-Like and Glucose-Dependent Insulinotropic Peptide to Create a Two-Component Drug for the Treatment of Type 2 Diabetes Mellitus and Obesity

2021 ◽  
Vol 37 (6) ◽  
pp. 74-83
Author(s):  
A.Yu. Gorbunova ◽  
E.P. Sannikova ◽  
I.I. Gubaidullin ◽  
O.M. Ignatova ◽  
M.Yu. Kopaeva ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mouse Model ◽  
Specific Activity ◽  
Two Component ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Insulinotropic Peptide

In addition to the previously developed recombinant modified human glucagon-like peptide 1 (rmglp1, Glypin), a recombinant modified human glucose-dependent insulinotropic peptide (RMGIP) has been obtained. A new universal reverse-phase HPLC technique has been proposed allowing quantitative analysis of rmGlp1 and rmGip separately and as part of a two-component preparation. The data show that the design of recombinant human rmGip according to the Glypine formula makes it possible to produce one-component and two-component preparations containing various rmGip and rmGlp1 protein ratios ranging from 1:0 to 20:1, using cell biomass samples mixed in predetermined proportions. Studies of human rmGip activity in a mouse model revealed reduced specific activity and signs of weak antagonistic effects. In this regard, there is a need for further study of human rmGip activity in a mouse model, including the use of alternative mouse or rat rmGip. type 2 diabetes mellitus; two-component drug, glucose-dependent insulinotropic peptide, glucagon-like peptide-1 The work was supported by the Internal Grant from National Research Center Kurchatov Institute.

scholarly journals Recombinant Human Insulin-Like Growth Factor-I Treatment Inhibits Gluconeogenesis in a Transgenic Mouse Model of Type 2 Diabetes Mellitus

Endocrinology ◽  
2006 ◽  
Vol 147 (6) ◽  
pp. 2619-2630 ◽  
Author(s):  
Patricia Pennisi ◽  
Oksana Gavrilova ◽  
Jennifer Setser-Portas ◽  
William Jou ◽  
Stefania Santopietro ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Growth Factor ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Recombinant Human Insulin ◽  
Factor I

scholarly journals Type 2 Diabetes Mellitus in Obese Mouse Model Induced by Monosodium Glutamate

2006 ◽  
Vol 55 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Mitsunobu NAGATA ◽  
Wataru SUZUKI ◽  
Seiichi IIZUKA ◽  
Masahiro TABUCHI ◽  
Hirofumi MARUYAMA ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mouse Model ◽  
Monosodium Glutamate ◽  
Obese Mouse

scholarly journals Apolipoprotein E deficiency abrogates insulin resistance in a mouse model of type 2 diabetes mellitus

Diabetologia ◽  
2009 ◽  
Vol 52 (7) ◽  
pp. 1434-1441 ◽  
Author(s):  
Y. Kawashima ◽  
J. Chen ◽  
H. Sun ◽  
D. Lann ◽  
R. J. Hajjar ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mouse Model ◽  
Apolipoprotein E

scholarly journals P4-522: TYPE 2 DIABETES MELLITUS INDUCES TAU-INDEPENDENT COGNITIVE AND SYNAPTIC DEFICITS IN A MOUSE MODEL

2019 ◽  
Vol 15 ◽  
pp. P1514-P1514
Author(s):  
Laura Trujillo-Estrada ◽  
Run R. Kuang ◽  
Celia Da Cunha ◽  
Stefania Forner ◽  
Alessandra Cadete Martini ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mouse Model

Hypoglycaemic effect of catalpol in a mouse model of high-fat diet-induced prediabetes

2020 ◽  
Vol 45 (10) ◽  
pp. 1127-1137 ◽  
Author(s):  
Dengqiu Xu ◽  
Xiaofei Huang ◽  
Hozeifa M. Hassan ◽  
Lu Wang ◽  
Sijia Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Mouse Model ◽  
Fasting Glucose ◽  
Hypoglycaemic Effect

Type 2 diabetes mellitus is a major health problem and a societal burden. Individuals with prediabetes are at increased risk of type 2 diabetes mellitus. Catalpol, an iridoid glycoside, has been reported to exert a hypoglycaemic effect in db/db mice, but its effect on the progression of prediabetes is unclear. In this study, we established a mouse model of prediabetes and examined the hypoglycaemic effect, and the mechanism of any such effect, of catalpol. Catalpol (200 mg/(kg·day)) had no effect on glucose tolerance or the serum lipid level in a mouse model of impaired glucose tolerance-stage prediabetes. However, catalpol (200 mg/(kg·day)) increased insulin sensitivity and decreased the fasting glucose level in a mouse model of impaired fasting glucose/impaired glucose tolerance-stage prediabetes. Moreover, catalpol increased the mitochondrial membrane potential (1.52-fold) and adenosine triphosphate content (1.87-fold) in skeletal muscle and improved skeletal muscle function. These effects were mediated by activation of the insulin receptor-1/glucose transporter type 4 (IRS-1/GLUT4) signalling pathway in skeletal muscle. Our findings will facilitate the development of a novel approach to suppressing the progression of diabetes at an early stage. Novelty Catalpol prevents the progression of prediabetes in a mouse model of prediabetes. Catalpol improves insulin sensitivity in skeletal muscle. The effects of catalpol are mediated by activation of the IRS-1/GLUT4 signalling pathway.

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