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      Overexpression of growth hormone improved hepatic glucose catabolism and relieved liver lipid deposition in common carp ( Cyprinus carpio L.) fed a high-starch diet

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          Abstract

          Growth hormone (GH) is important for regulating insulin secretion and carbohydrate metabolism, and its role in mammalian models of diabetes is relatively worked out. Although some fish species were used as models for diabetes research, the effects of GH on insulin and glucose catabolism and anabolism in these models remain to be clarified. In this study, we investigated the effect of GH on insulin and glucose catabolism and anabolism in an omnivorous fish using GH transgenic (T) common carp that consistently overexpressed GH and wild-type (WT) common carp. We compared the intestinal morphology, and digestive and absorptive capacity of fish fed commercial feed. We also analyzed the growth performance, insulin level, glucose catabolism and anabolism, lipid deposition, and lipid catabolism and anabolism in T carp and WT carp fed diets containing either 30% or 40% starch. In the intestine of T carp, α-amylase activity was enhanced, the number of goblet cells and intestinal villi surface area was increased, and the expression level of glucose transport protein-related genes ( glut2 and sglt1) was upregulated when compared to these indicators in WT carp. When fed either a normal or high-starch diet, the growth performance of T carp was better than that of WT carp. Compared with WT carp, serum insulin was increased and glucose was decreased, hepatic expression level of igf-1 and glycolysis-related genes was increased, and the activity level of a hepatic enzyme related to glycolysis was enhanced in T carp. When fed with a high-starch diet, the serum alanine aminotransferase activity, hepatic lipid content, and malondialdehyde content were significantly lower in T carp than in WT carp. These results indicated that overexpression of GH (1) enhanced carbohydrate digestion and absorption in the carp intestine, (2) did not induce insulin resistance and improved glucose catabolism and utilization in carp, and (3) relieved liver lipid deposition. Our data might provide new insights into potential ways to improve glucose utilization in fish and diabetes treatments.

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          Most cited references37

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          A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES

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            Insulin resistance in cavefish as an adaptation to a nutrient-limited environment

            Periodic food shortages are a major challenge faced by organisms in natural habitats. Cave-dwelling animals must withstand long periods of nutrient deprivation, as-in the absence of photosynthesis-caves depend on external energy sources such as seasonal floods. Here we show that cave-adapted populations of the Mexican tetra, Astyanax mexicanus, have dysregulated blood glucose homeostasis and are insulin-resistant compared to river-adapted populations. We found that multiple cave populations carry a mutation in the insulin receptor that leads to decreased insulin binding in vitro and contributes to hyperglycaemia. Hybrid fish from surface-cave crosses carrying this mutation weigh more than non-carriers, and zebrafish genetically engineered to carry the mutation have increased body weight and insulin resistance. Higher body weight may be advantageous in caves as a strategy to cope with an infrequent food supply. In humans, the identical mutation in the insulin receptor leads to a severe form of insulin resistance and reduced lifespan. However, cavefish have a similar lifespan to surface fish and do not accumulate the advanced glycation end-products in the blood that are typically associated with the progression of diabetes-associated pathologies. Our findings suggest that diminished insulin signalling is beneficial in a nutrient-limited environment and that cavefish may have acquired compensatory mechanisms that enable them to circumvent the typical negative effects associated with failure to regulate blood glucose levels.
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              A quick look at biochemistry: carbohydrate metabolism.

              In mammals, there are different metabolic pathways in cells that break down fuel molecules to transfer their energy into high energy compounds such as adenosine-5'-triphosphate (ATP), guanosine-5'-triphosphate (GTP), reduced nicotinamide adenine dinucleotide (NADH2), reduced flavin adenine dinucleotide (FADH2) and reduced nicotinamide adenine dinucleotide phosphate (NADPH2). This process is called cellular respiration. In carbohydrate metabolism, the breakdown starts from digestion of food in the gastrointestinal tract and is followed by absorption of carbohydrate components by the enterocytes in the form of monosaccharides. Monosaccharides are transferred to cells for aerobic and anaerobic respiration via glycolysis, citric acid cycle and pentose phosphate pathway to be used in the starvation state. In the normal state, the skeletal muscle and liver cells store monosaccharides in the form of glycogen. In the obesity state, the extra glucose is converted to triglycerides via lipogenesis and is stored in the lipid droplets of adipocytes. In the lipotoxicity state, the lipid droplets of other tissues such as the liver, skeletal muscle and pancreatic beta cells also accumulate triacylglycerol. This event is the axis of the pathogenesis of metabolic dysregulation in insulin resistance, metabolic syndrome and type 2 diabetes. In this paper a summary of the metabolism of carbohydrates is presented in a way that researchers can follow the biochemical processes easily. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                06 December 2022
                2022
                : 13
                : 1038479
                Affiliations
                [1] 1 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Hubei Hongshan Laboratory , Wuhan, China
                [2] 2 College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences , Beijing, China
                [3] 3 School of Basic Medical Science, Wuhan University , Wuhan, China
                [4] 4 Qingdao National Laboratory for Marine Science and Technology , Qingdao, China
                Author notes

                Edited by: Wensheng Li, Sun Yat-sen University, China

                Reviewed by: Laura Ellestad, University of Georgia, United States; Shan He, Huazhong Agricultural University, China

                *Correspondence: Wei Hu, huwei@ 123456ihb.ac.cn ; Ji Chen, chenji@ 123456ihb.ac.cn

                This article was submitted to Experimental Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2022.1038479
                9763934
                36561570
                fb253f93-1658-4c96-9d58-2c3644699a6d
                Copyright © 2022 Wu, Li, Wu, Guo, Zhong, Li, Song, Tao, Chen, Han, Xie, Wang, Zhu and Hu

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 07 September 2022
                : 14 November 2022
                Page count
                Figures: 10, Tables: 0, Equations: 5, References: 38, Pages: 14, Words: 6708
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 31721005, 31672661
                Funded by: State Key Laboratory of Freshwater Ecology and Biotechnology , doi 10.13039/501100011223;
                Award ID: 2022FBZ03
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                growth hormone overexpression,insulin sensitivity,glucose utilization,liver lipid deposition,common carp (cyprinus carpio l.)

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