Interaction of B0AT1 Deficiency and Diet on Metabolic Function and Diabetes Incidence in Male Nonobese Diabetic Mice.

IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Matthew F Waters, Viviane Delghingaro-Augusto, Muhammad Shamoon, Kiran Javed, Gaetan Burgio, Jane E Dahlstrom, Stefan Bröer, Christopher J Nolan
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引用次数: 0

Abstract

Context: The obesity epidemic parallels an increasing type 1 diabetes incidence, such that westernized diets, containing high fat, sugar, and/or protein, through inducing nutrient-induced islet β-cell stress, have been proposed as contributing factors. The broad-spectrum neutral amino acid transporter (B0AT1), encoded by Slc6a19, is the major neutral amino acids transporter in intestine and kidney. B0AT1 deficiency in C567Bl/6J mice causes aminoaciduria, lowers insulinemia, and improves glucose tolerance.

Objective: We investigated the effects of standard rodent chow (chow), high-fat high-sucrose (HFHS), and high-fat high-protein (HFHP) diets, in addition to B0AT1 deficiency, on the diabetes incidence of male nonobese diabetic (NOD/ShiLtJArc (NOD)) mice.

Methods: Male NOD.Slc6a19+/+ and NOD.Slc6a19-/- mice were fed chow, HFHS and HFHP diets from 6 to 24 weeks of age. A separate cohort of male NOD mice were fed the three diets from 6-30 weeks of age. Body weight and fed-state blood glucose and plasma insulin were monitored, and urinary amino-acid profiles, intraperitoneal glucose tolerance, diabetes incidence, pancreatic islet number, insulitis scores and beta-cell mass were measured.

Results: The incidence of diabetes and severe glucose intolerance was 3.8% in HFHS-fed, 25.0% in HFHP-fed, and 14.7% in chow-fed mice, with higher pancreatic islet number and lower insulitis scores in HFHS-fed mice. B0AT1 deficiency had no effect on diabetes incidence, but curtailed HFHS-induced excessive weight gain, adipose tissue expansion, and hyperinsulinemia. In HFHP-fed mice, B0AT1 deficiency significantly increased pancreatic β-cell clusters and small islets. Male NOD mice that did not develop autoimmune diabetes were resistant to diet-induced hyperglycemia.

Conclusion: Dietary composition does, but B0AT1 deficiency does not, affect autoimmune diabetes incidence in male NOD mice. B0AT1 deficiency, however, reduces diet-induced metabolic dysfunction and in HFHP-fed mice increases pancreatic β-cell clusters and small islets.

B0AT1缺乏与饮食对NOD雄性小鼠代谢功能和糖尿病发病率的相互作用
背景:肥胖的流行与1型糖尿病发病率的增加是平行的,例如,西方化的饮食,含有高脂肪、糖和/或蛋白质,通过诱导营养诱导的胰岛β细胞应激,被认为是促成因素。由Slc6a19编码的广谱中性氨基酸转运蛋白(B0AT1)是肠道和肾脏中主要的中性氨基酸转运蛋白。C567Bl/6J小鼠B0AT1缺乏,引起氨基酸尿症,降低胰岛素血症,提高葡萄糖耐量。目的:研究标准鼠粮(chow)、高脂高糖(HFHS)和高脂高蛋白(HFHP)日粮以及缺乏B0AT1对雄性非肥胖糖尿病(NOD/ShiLtJArc (NOD))小鼠糖尿病发病率的影响。结果:糖尿病和严重糖耐量不良的发生率分别为:hfhs组3.8%、25.0%和14.7%,且hfhs组胰岛数目较高、胰岛素评分较低。B0AT1缺乏对糖尿病发病率没有影响,但可以减少hfhs引起的过度体重增加、脂肪组织扩张和高胰岛素血症。在hfhp喂养的小鼠中,B0AT1缺乏显著增加了胰腺β细胞簇和小胰岛。未发生自身免疫性糖尿病的雄性NOD小鼠对饮食诱导的高血糖有抵抗力。结论:膳食成分对雄性NOD小鼠自身免疫性糖尿病发病率有影响,但B0AT1缺乏对其无影响。然而,B0AT1缺乏减少饮食引起的代谢功能障碍,并且在HFHP喂养的小鼠中增加胰腺β细胞簇和小胰岛。
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来源期刊
Endocrinology
Endocrinology 医学-内分泌学与代谢
CiteScore
8.10
自引率
4.20%
发文量
195
审稿时长
2-3 weeks
期刊介绍: The mission of Endocrinology is to be the authoritative source of emerging hormone science and to disseminate that new knowledge to scientists, clinicians, and the public in a way that will enable "hormone science to health." Endocrinology welcomes the submission of original research investigating endocrine systems and diseases at all levels of biological organization, incorporating molecular mechanistic studies, such as hormone-receptor interactions, in all areas of endocrinology, as well as cross-disciplinary and integrative studies. The editors of Endocrinology encourage the submission of research in emerging areas not traditionally recognized as endocrinology or metabolism in addition to the following traditionally recognized fields: Adrenal; Bone Health and Osteoporosis; Cardiovascular Endocrinology; Diabetes; Endocrine-Disrupting Chemicals; Endocrine Neoplasia and Cancer; Growth; Neuroendocrinology; Nuclear Receptors and Their Ligands; Obesity; Reproductive Endocrinology; Signaling Pathways; and Thyroid.
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