scholarly journals Senescence Marker Protein-30/Gluconolactonase Deletion Worsens Glucose Tolerance through Impairment of Acute Insulin Secretion

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 529-536 ◽  
Author(s):  
Goji Hasegawa ◽  
Masahiro Yamasaki ◽  
Mayuko Kadono ◽  
Muhei Tanaka ◽  
Mai Asano ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Cell Mass ◽  
Tolerance Test ◽  
Distal Portion ◽  
Marker Protein ◽  
High Fat ◽  
Glucose Levels ◽  
Age Related

Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with age. We recently identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonase (GNL), which is involved in vitamin C biosynthesis in animal species. To examine whether the age-related decrease in SMP30/GNL has effects on glucose homeostasis, we used SMP30/GNL knockout (KO) mice treated with l-ascorbic acid. In an ip glucose tolerance test at 15 wk of age, blood glucose levels in SMP30/GNL KO mice were significantly increased by 25% at 30 min after glucose administration compared with wild-type (WT) mice. Insulin levels in SMP30/GNL KO mice were significantly decreased by 37% at 30 min after glucose compared with WT mice. Interestingly, an insulin tolerance test showed a greater glucose-lowering effect in SMP30/GNL KO mice. High-fat diet feeding severely worsened glucose tolerance in both WT and SMP30/GNL KO mice. Morphometric analysis revealed no differences in the degree of high-fat diet-induced compensatory increase in β-cell mass and proliferation. In the static incubation study of islets, insulin secretion in response to 20 mm glucose or KCl was significantly decreased in SMP30/GNL KO mice. On the other hand, islet ATP content at 20 mm in SMP30/GNL KO mice was similar to that in WT mice. Collectively, these data indicate that impairment of the early phase of insulin secretion due to dysfunction of the distal portion of the secretion pathway underlies glucose intolerance in SMP30/GNL KO mice. Decreased SMP30/GNL may contribute to the worsening of glucose tolerance that occurs in normal aging.

scholarly journals Dietary sodium chloride attenuates increased β-cell mass to cause glucose intolerance in mice under a high-fat diet

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248065
Author(s):  
Keigo Taki ◽  
Hiroshi Takagi ◽  
Tomonori Hirose ◽  
Runan Sun ◽  
Hiroshi Yaginuma ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Plasma Glucose ◽  
High Fat Diet ◽  
Cell Mass ◽  
Tolerance Test ◽  
Chow Diet ◽  
High Fat ◽  
Lower Plasma ◽  
Β Cell

Excessive sodium salt (NaCl) or fat intake is associated with a variety of increased health risks. However, whether excessive NaCl intake accompanied by a high-fat diet (HFD) affects glucose metabolism has not been elucidated. In this study, C57BL/6J male mice were fed a normal chow diet (NCD), a NCD plus high-NaCl diet (NCD plus NaCl), a HFD, or a HFD plus high-NaCl diet (HFD plus NaCl) for 30 weeks. No significant differences in body weight gain, insulin sensitivity, and glucose tolerance were observed between NCD-fed and NCD plus NaCl-fed mice. In contrast, body and liver weights were decreased, but the weight of epididymal white adipose tissue was increased in HFD plus NaCl-fed compared to HFD-fed mice. HFD plus NaCl-fed mice had lower plasma glucose levels in an insulin tolerance test, and showed higher plasma glucose and lower plasma insulin levels in an intraperitoneal glucose tolerance test compared to HFD-fed mice. The β-cell area and number of islets were decreased in HFD plus NaCl-fed compared to HFD-fed mice. Increased Ki67-positive β-cells, and increased expression levels of Ki67, CyclinB1, and CyclinD1 mRNA in islets were observed in HFD-fed but not HFD plus NaCl-fed mice when compared to NCD-fed mice. Our data suggest that excessive NaCl intake accompanied by a HFD exacerbates glucose intolerance, with impairment in insulin secretion caused by the attenuation of expansion of β-cell mass in the pancreas.

scholarly journals Palmatine ameliorates high fat diet induced impaired glucose tolerance

2020 ◽  
Vol 53 (1) ◽  
Author(s):  
Xusheng Tian ◽  
Yukun Zhang ◽  
Han Li ◽  
Yunfeng Li ◽  
Ning Wang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Cell Apoptosis ◽  
High Fat Diet ◽  
Cell Mass ◽  
Mapk Signaling ◽  
High Fat ◽  
Β Cell

Abstract Background The impaired glucose tolerance (IGT) is a representative prediabetes characterized by defective glucose homeostasis, and palmatine (PAL) is a natural isoquinoline alkaloid with multiple pharmacological effects. Our study aims to investigate the therapeutic effect of PAL on the impaired glucose tolerance. Methods Male Sprague–Dawley rats were used to establish an IGT model with high fat diet (HFD). Oral glucose tolerance test (OGTT) and further biochemical analysis were conducted to determine the effect of PAL on glucose intolerance in vivo. Molecular details were clarified in a cellular model of IGT induced by Palmitate (PA) on INS-1 cells. Results Our study demonstrated a relief of IGT with improved insulin resistance in HFD induced rats after PAL treatment. Besides, promoted pancreas islets function was validated with significantly increased β cell mass after the treatment of PAL. We further found out that PAL could alleviate the β cell apoptosis that accounts for β cell mass loss in IGT model. Moreover, MAPK signaling was investigated in vivo and vitro with the discovery that PAL regulated the MAPK signaling by restricting the ERK and JNK cascades. The insulin secretion assay indicated that PAL significantly promoted the defective insulin secretion in PA-induced INS-1 cells via JNK rather than ERK signaling. Furthermore, PAL treatment was determined to significantly suppress β cell apoptosis in PA-induced cells. We thus thought that PAL promoted the PA-induced impaired insulin release by inhibiting the β cell apoptosis and JNK signaling in vitro. Conclusion In summary, PAL ameliorates HFD-induced IGT with novel mechanisms.

scholarly journals Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Camila Lubaczeuski ◽  
Luciana Mateus Gonçalves ◽  
Jean Franciesco Vettorazzi ◽  
Mirian Ayumi Kurauti ◽  
Junia Carolina Santos-Silva ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Insulin Clearance ◽  
Protein Diet ◽  
Low Protein Diet ◽  
High Fat ◽  
Insulin Degrading Enzyme ◽  
Low Protein

The aim of this study was to investigate the effect of subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early in life, followed by exposure to a high-fat diet in adulthood. Weaned 30-day-old C57Bl/6 mice were submitted to a low-protein diet (6% protein). After 4 weeks, the mice were distributed into three groups: LP group, which continued receiving a low-protein diet; LP + HF group, which started to receive a high-fat diet; and LP + HFvag group, which underwent vagotomy and also was kept at a high-fat diet. Glucose-stimulated insulin secretion (GSIS) in isolated islets, ipGTT, ipITT, in vivo insulin clearance, and liver expression of the insulin-degrading enzyme (IDE) was accessed. Vagotomy improved glucose tolerance and reduced insulin secretion but did not alter adiposity and insulin sensitivity in the LP + HFvag, compared with the LP + HF group. Improvement in glucose tolerance was accompanied by increased insulinemia, probably due to a diminished insulin clearance, as judged by the lower C-peptide : insulin ratio, during the ipGTT. Finally, vagotomy also reduced liver IDE expression in this group. In conclusion, when submitted to vagotomy, the metabolic programmed mice showed improved glucose tolerance, associated with an increase of plasma insulin concentration as a result of insulin clearance reduction, a phenomenon probably due to diminished liver IDE expression.

scholarly journals Hypoglycemic effects and mechanisms of electroacupuncture on insulin resistance

2014 ◽  
Vol 307 (3) ◽  
pp. R332-R339 ◽  
Author(s):  
Jieyun Yin ◽  
Jian Kuang ◽  
Manisha Chandalia ◽  
Demidmaa Tuvdendorj ◽  
Batbayar Tumurbaatar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Free Fatty Acid ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
High Fat

The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on blood glucose and insulin sensitivity in mice fed a high-fat diet. Both wild-type (WT) and adipose ectonucleotide pyrophosphate phosphodiesterase (ENPP1) transgenic (TG) mice were fed a high-fat diet for 12 wk; for each mouse, an intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed with or without EA at abdomen or auricular areas. A high-fat diet-induced insulin resistance in both WT and TG mice. In the WT mice, EA at 3 Hz and 15 Hz, but not at 1 Hz or 100 Hz, via CV4+CV12 significantly reduced postprandial glucose levels; EA at 3 Hz was most potent. The glucose level was reduced by 61.7% at 60 min and 74.5% at 120 min with EA at 3 Hz (all P < 0.001 vs. control). Similar hypoglycemic effect was noted in the TG mice. On the contrary, EA at auricular points increased postprandial glucose level ( P < 0.03). 4). EA at 3 Hz via CV4+CV12 significantly enhanced the decrease of blood glucose after insulin injection, suggesting improvement of insulin sensitivity. Plasma free fatty acid was significantly suppressed by 42.5% at 15 min and 50.8% at 30 min with EA ( P < 0.01) in both WT and TG mice. EA improves glucose tolerance in both WT and TG mice fed a high-fat diet, and the effect is associated with stimulation parameters and acupoints and is probably attributed to the reduction of free fatty acid.

scholarly journals APP deficiency results in resistance to obesity but impairs glucose tolerance upon high fat feeding

2018 ◽  
Vol 237 (3) ◽  
pp. 311-322 ◽  
Author(s):  
Juliane K Czeczor ◽  
Amanda J Genders ◽  
Kathryn Aston-Mourney ◽  
Timothy Connor ◽  
Liam G Hall ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Glucose Tolerance ◽  
Cell Mass ◽  
Tolerance Test ◽  
Whole Body ◽  
Dark Phase ◽  
High Fat ◽  
Neuronal Metabolism ◽  
Fat Feeding ◽  
Deficient Mice

The amyloid precursor protein (APP) generates a number of peptides when processed through different cleavage mechanisms, including the amyloid beta peptide that is implicated in the development of Alzheimer’s disease. It is well established that APP via its cleaved peptides regulates aspects of neuronal metabolism. Emerging evidence suggests that amyloidogenic processing of APP can lead to altered systemic metabolism, similar to that observed in metabolic disease states. In the present study, we investigated the effect of APP deficiency on obesity-induced alterations in systemic metabolism. Compared with WT littermates, APP-deficient mice were resistant to diet-induced obesity, which was linked to higher energy expenditure and lipid oxidation throughout the dark phase and was associated with increased spontaneous physical activity. Consistent with this lean phenotype, APP-deficient mice fed a high-fat diet (HFD) had normal insulin tolerance. However, despite normal insulin action, these mice were glucose intolerant, similar to WT mice fed a HFD. This was associated with reduced plasma insulin in the early phase of the glucose tolerance test. Analysis of the pancreas showed that APP was required to maintain normal islet and β-cell mass under high fat feeding conditions. These studies show that, in addition to regulating aspects of neuronal metabolism, APP is an important regulator of whole body energy expenditure and glucose homeostasis under high fat feeding conditions.

scholarly journals Intravenous Glutamine Administration Improves Glucose Tolerance and Attenuates the Inflammatory Response in Diet-Induced Obese Mice after Sleeve Gastrectomy

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3192
Author(s):  
Chiu-Li Yeh ◽  
Po-Jen Yang ◽  
Po-Chu Lee ◽  
Jin-Ming Wu ◽  
Po-Da Chen ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Sleeve Gastrectomy ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Macrophage Infiltration ◽  
Obese Mice ◽  
High Fat ◽  
Glucose Levels ◽  
Elevated Glucose ◽  
Cluster Of Differentiation

Obesity is a health problem associated with many metabolic disorders. Weight reduction can effectively alleviate obesity-associated complications. Sleeve gastrectomy is a commonly used bariatric surgery and is considered safe and effective for improving outcomes. Glutamine (GLN) is an amino acid with anti-oxidative and anti-inflammatory properties. This study used a mouse model of sleeve gastrectomy to investigate the impacts of intravenous GLN administration on glucose tolerance and adipocyte inflammation short-term after surgery. C57BL6 male mice were divided into normal control (NC) and high-fat diet groups. The high-fat diet provided 60% of energy from fat for 10 weeks to induce obesity. Mice fed the high-fat diet were then assigned to a sham (SH) or sleeve gastrectomy with saline (S) or GLN (G) groups. The S group was intravenously injected with saline, while the G group was administered GLN (0.75 g/kg body weight) via a tail vein postoperatively. Mice in the experimental groups were sacrificed on day 1 or 3 after the surgery. Results showed that obesity resulted in fat accumulation, elevated glucose levels, and adipokines production. Sleeve gastrectomy aggravated expressions of inflammatory cytokine and macrophage infiltration markers, cluster of differentiation 68 (CD68), epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR-1), and macrophage chemoattractant protein-1, in adipose tissues. Treatment of obese mice with GLN downregulated hepatic proteomic profiles associated with the gluconeogenesis pathway and improved glucose tolerance. Moreover, macrophage infiltration and adipose tissue inflammation were attenuated after the sleeve gastrectomy. These findings imply that postoperative intravenous GLN administration may improve glucose tolerance and attenuate inflammation shortly after the bariatric surgery in subjects with obesity.

scholarly journals Modifications of gastric inhibitory polypeptide (GIP) secretion in man by a high-fat diet

1988 ◽  
Vol 59 (3) ◽  
pp. 373-380 ◽  
Author(s):  
L. M. Morgan ◽  
S. M. Hampton ◽  
J. A. Tredger ◽  
R. Cramb ◽  
V. Marks
Keyword(s):  
Glucose Tolerance ◽  
Energy Intake ◽  
Plasma Glucose ◽  
High Fat Diet ◽  
Gastric Inhibitory Polypeptide ◽  
Oral Glucose ◽  
Fat Intake ◽  
High Fat ◽  
C Peptide ◽  
Glucose Levels

1. Five healthy volunteers (usual fat intake 103) (SE 9) g/d and energy intake 9855 (SE 937) kJ/d were given on two separate occasions (a) 100 g oral glucose and (b) sufficient intravenous (IV) glucose to obtain similar arterialized plasma glucose levels to those after oral glucose.2. Subjects increased their fat intake by 68 (SE 9·6) % for 28 d by supplementing their diet with 146 ml double cream/d (fat intake on high-fat diet (HFD) 170 (SE 8) g/d; energy intake 12347 (SE 770)).3. The 100 g oral glucose load was repeated and IV glucose again given in quantities sufficient to obtain similar arterialized blood glucose levels. Immunoreactive plasma insulin, C-peptide and gastric inhibitory polypeptide (GIP) were measured.4. Plasma GIP levels were higher following oral glucose after the HFD (area under plasma GIP curve 0–180 min 1660 (SE 592) v. 2642 (SE 750) ng/l.h for control and HFD respectively; P < 0·05). Both insulin and C-peptide levels were significantly higher after oral than after IV glucose (P < 0·01) but neither were affected by the HFD. Glucose levels were lower following the HFD after both oral and IV glucose (area under plasma glucose curve 0–180 min, following oral glucose 6·7 (SE 0·3) mmol/l.h for control and 4·2 (SE 0·6) mmol/l.h for HFD; P < 0·01).5. Glucose-stimulated GIP secretion was thus enhanced by the HFD. Insulin secretion in response to oral glucose was unchanged, in spite of an improvement in glucose tolerance.6. The improvement in glucose tolerance post-HFD could possibly be due to a GIP-mediated inhibition of hepatic glycogenolysis, or a decreased rate of glucose uptake from the small intestine.

scholarly journals β-cell knockout of SENP1 reduces responses to incretins and worsens oral glucose tolerance in high fat diet-fed mice

2021 ◽  
Author(s):  
Haopeng Lin ◽  
Nancy Smith ◽  
Aliya F Spigelman ◽  
Kunimasa Suzuki ◽  
Mourad Ferdaoussi ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Glucagon Secretion ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
High Fat ◽  
Β Cell ◽  
Islet Mass

SUMOylation reduces oxidative stress and preserves islet mass at the expense of robust insulin secretion. To investigate a role for the deSUMOylating enzyme <u>sen</u>trin-specific <u>p</u>rotease <u>1</u> (SENP1) following metabolic stress, we put pancreas/gut-specific SENP1 knockout mice (pSENP1-KO) on a high fat diet (HFD). Male pSENP1-KO mice were more glucose intolerant following HFD than littermate controls, but only in response to oral glucose. A similar phenotype was observed in females. Plasma glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide 1 (GLP-1) responses were identical in pSENP1-KO and -WT littermates, including the HFD-induced upregulation of GIP responses. Islet mass was not different, but insulin secretion and β-cell exocytotic responses to the GLP-1 receptor agonist Exendin-4 (Ex4) and GIP were impaired in islets lacking SENP1. Glucagon secretion from pSENP1-KO islets was also reduced, so we generated β-cell-specific SENP1 knockout mice (βSENP1-KO). These phenocopied the pSENP1-KO mice with selective impairment in oral glucose tolerance following HFD, preserved islet mass expansion, and impaired β-cell exocytosis and insulin secretion to Ex4 and GIP without changes in cAMP or Ca<sup>2+</sup> levels. Thus, β-cell SENP1 limits oral glucose intolerance following HFD by ensuring robust insulin secretion at a point downstream of incretin signaling.

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