Mice lacking the proton channel Hv1 exhibit a sex-specific differences in glucose homeostasis

Insulin secretion by pancreatic islet β-cells is regulated by glucose levels and is accompanied by proton generation. The voltage-gated proton channel Hv1 is present in pancreatic β-cells and extremely selective for protons. However, whether Hv1 is involved in insulin secretion is unclear. Here we demonstrate that Hv1 promotes insulin secretion of pancreatic β-cells and glucose homeostasis. Hv1-deficient mice displayed hyperglycemia and glucose intolerance because of reduced insulin secretion but retained normal peripheral insulin sensitivity. Moreover, Hv1 loss contributed much more to severe glucose intolerance as the mice got older. Islets of Hv1-deficient and heterozygous mice were markedly deficient in glucose- and K+-induced insulin secretion. In perifusion assays, Hv1 deletion dramatically reduced the first and second phase of glucose-stimulated insulin secretion. Islet insulin and proinsulin content was reduced, and histological analysis of pancreas slices revealed an accompanying modest reduction of β-cell mass in Hv1 knockout mice. EM observations also indicated a reduction in insulin granule size, but not granule number or granule docking, in Hv1-deficient mice. Mechanistically, Hv1 loss limited the capacity for glucose-induced membrane depolarization, accompanied by a reduced ability of glucose to raise Ca2+ levels in islets, as evidenced by decreased durations of individual calcium oscillations. Moreover, Hv1 expression was significantly reduced in pancreatic β-cells from streptozotocin-induced diabetic mice, indicating that Hv1 deficiency is associated with β-cell dysfunction and diabetes. We conclude that Hv1 regulates insulin secretion and glucose homeostasis through a mechanism that depends on intracellular Ca2+ levels and membrane depolarization.

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Supplementation with beta-hydroxy-beta-methylbutyrate impacts glucose homeostasis and increases liver size in trained mice

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000445 ◽

2020 ◽

Vol 90 (1-2) ◽

pp. 113-123

Author(s):

Ines Schadock ◽

Barbara G. Freitas ◽

Irae L. Moreira ◽

Joao A. Rincon ◽

Marcio Nunes Correa ◽

...

Keyword(s):

Strength Training ◽

Muscle Mass ◽

Glucose Homeostasis ◽

Fasting Blood Glucose ◽

Hepatic Metabolism ◽

Mass Gain ◽

Trained Group ◽

Tissue Mass ◽

Liver Size ◽

Intensive Training

Abstract. β-hydroxy-β-methyl butyrate (HMB) is a bioactive metabolite derived from the amino acid leucine, usually applied for muscle mass increase during physical training, as well as for muscle mass maintenance in debilitating chronic diseases. The hypothesis of the present study is that HMB is a safe supplement for muscle mass gain by strength training. Based on this, the objective was to measure changes in body composition, glucose homeostasis and hepatic metabolism of HMB supplemented mice during strength training. Two of four groups of male mice (n = 6/group) underwent an 8-week training period session (climbing stairs) with or without HMB supplementation (190 mg/kgBW per day). We observed lower body mass gain (4.9 ± 0.43% versus 1.2 ± 0.43, p < 0.001) and increased liver mass (40.9 ± 0.9 mg/gBW versus 44.8 ± 1.3, p < 0.001) in the supplemented trained group compared with the non-supplemented groups. The supplemented trained group had an increase in relative adipose tissue mass (12.4 ± 0.63 mg/gBW versus 16.1 ± 0.88, P < 0.01) compared to the non-supplemented untrained group, and an increase in fasting blood glucose (111 ± 4.58 mg/dL versus 122 ± 3.70, P < 0.05) and insulin resistance (3.79 ± 0.19 % glucose decay/min versus 2.45 ± 0.28, P < 0.05) comparing with non-supplemented trained group. Adaptive heart hypertrophy was observed only in the non-supplemented trained group (4.82 ± 0.05 mg/gBW versus 5.12 ± 0.13, P < 0.05). There was a higher hepatic insulin-like growth factor-1 expression (P = 0.002) in supplemented untrained comparing with non-supplemented untrained group. Gene expression of gluconeogenesis regulatory factors was increased by training and reduced by HMB supplementation. These results confirm that HMB supplementation associated with intensive training protocol drives changes in glucose homeostasis and liver metabolism in mice.

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Glucose homeostasis: Sugar boost

Nature China ◽

10.1038/nchina.2008.228 ◽

2008 ◽

Author(s):

Felix Cheung

Keyword(s):

Glucose Homeostasis

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FGF21 improves glucose homeostasis in diabetes-prone NZO mice

Diabetologie und Stoffwechsel ◽

10.1055/s-0037-1601632 ◽

2017 ◽

Vol 12 (S 01) ◽

pp. S1-S84

Author(s):

T Laeger ◽

C Baumeier ◽

J Würfel ◽

A Schürmann

Keyword(s):

Glucose Homeostasis ◽

Nzo Mice

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Studies of Nuf mice with an activating calcium-sensing receptor (CaSR) mutation demonstrate the CaSR to regulate pancreatic beta-cell mass and glucose homeostasis

Endocrine Abstracts ◽

10.1530/endoabs.38.p186 ◽

2015 ◽

Author(s):

Valerie N Babinsky ◽

Fadil M Hannan ◽

M Andrew Nesbit ◽

Alison Hough ◽

Michelle Stewart ◽

...

Keyword(s):

Beta Cell ◽

Glucose Homeostasis ◽

Pancreatic Beta Cell ◽

Cell Mass ◽

Beta Cell Mass ◽

Calcium Sensing Receptor ◽

Calcium Sensing ◽

Pancreatic Beta Cell Mass

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Thermoneutral housing does not influence fat mass or glucose homeostasis in C57BL/6 mice

Journal of Endocrinology ◽

10.1530/joe-18-0279 ◽

2018 ◽

Vol 239 (3) ◽

pp. 313-324 ◽

Cited By ~ 9

Author(s):

Lewin Small ◽

Henry Gong ◽

Christian Yassmin ◽

Gregory J Cooney ◽

Amanda E Brandon

Keyword(s):

Glucose Metabolism ◽

Ambient Temperature ◽

Fat Mass ◽

Glucose Homeostasis ◽

Dietary Intervention ◽

Whole Body ◽

Housing Temperature ◽

Brown Adipose ◽

Normal Chow ◽

Obesogenic Diet

One major factor affecting physiology often overlooked when comparing data from animal models and humans is the effect of ambient temperature. The majority of rodent housing is maintained at ~22°C, the thermoneutral temperature for lightly clothed humans. However, mice have a much higher thermoneutral temperature of ~30°C, consequently data collected at 22°C in mice could be influenced by animals being exposed to a chronic cold stress. The aim of this study was to investigate the effect of housing temperature on glucose homeostasis and energy metabolism of mice fed normal chow or a high-fat, obesogenic diet (HFD). Male C57BL/6J(Arc) mice were housed at standard temperature (22°C) or at thermoneutrality (29°C) and fed either chow or a 60% HFD for 13 weeks. The HFD increased fat mass and produced glucose intolerance as expected but this was not exacerbated in mice housed at thermoneutrality. Changing the ambient temperature, however, did alter energy expenditure, food intake, lipid content and glucose metabolism in skeletal muscle, liver and brown adipose tissue. Collectively, these findings demonstrate that mice regulate energy balance at different housing temperatures to maintain whole-body glucose tolerance and adiposity irrespective of the diet. Despite this, metabolic differences in individual tissues were apparent. In conclusion, dietary intervention in mice has a greater impact on adiposity and glucose metabolism than housing temperature although temperature is still a significant factor in regulating metabolic parameters in individual tissues.

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