A short review on the features of the non-obese diabetic Goto-Kakizaki rat intestine

Gimenes, G.M.; Santana, G.O.; Scervino, M.V.M.; Curi, R.; Pereira, J.N.B.

doi:10.1590/1414-431X2022e11910

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Brazilian Journal of Medical and Biological Research

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Review • Braz. J. Med. Biol. Res. 55 • 2022 • https://doi.org/10.1590/1414-431X2022e11910 copy

A short review on the features of the non-obese diabetic Goto-Kakizaki rat intestine

Authorship SCIMAGO INSTITUTIONS RANKINGS

The Goto-Kakizaki (GK) rat is a non-obese experimental model of type 2 diabetes mellitus (T2DM) that allows researchers to monitor diabetes-induced changes without jeopardizing the effects of obesity. This rat strain exhibits notable gastrointestinal features associated with T2DM, such as marked alterations in intestinal morphology, reduced intestinal motility, slow transit, and modified microbiota compared to Wistar rats. The primary treatments for diabetic patients include administration of hypoglycemic agents and insulin, and lifestyle changes. Emerging procedures, including alternative therapies, metabolic surgeries, and modulation of the intestinal microbiota composition, have been shown to improve the diabetic state of GK rats. This review describes the morpho-physiological diabetic-associated features of the gastrointestinal tract (GIT) of GK rats. We also describe promising strategies, e.g., metabolic surgery and modulation of gut microbiota composition, used to target the GIT of this animal model to improve the diabetic state.

Gastrointestinal tract; Type 2 diabetes; GK rats; Intestinal microbiota; Diabetes treatment

Reference	Procedure	Study length	Final age	Body weight	Main findings
Qiao et al., 2018 (⁶⁴64. Qiao Z, Han J, Feng H, Zheng H, Wu J, Gao C, et al. Fermentation products of Paenibacillus bovis sp. nov. BD3526 alleviates the symptoms of type 2 diabetes mellitus in GK rats. Front Microbiol 2019; 10: 3292, doi: 10.3389/fmicb.2018.03292. https://doi.org/10.3389/fmicb.2018.03292... )	Supplementation with Paenibacillus bovis sp. nov. BD3526	8 weeks	21 weeks old	↓	↓ HbA1C; ↑ microbiota diversity at weeks 2 and 3, which was restored after 6 weeks; ↔ SCFA-producing bacteria.
Zhao et al., 2018 (⁶⁵65. Zhao L, Chen Y, Xia F, Abudukerimu B, Zhang W, Guo Y, et al. A glucagon-like peptide-1 receptor agonist lowers weight by modulating the structure of gut microbiota. Front Endocrinol (Lausanne) 2018; 9: 233, doi: 10.3389/fendo.2018.00233. https://doi.org/10.3389/fendo.2018.00233... )	HFD and liraglutide injection	8 weeks of HFD and 12 weeks of injection	24 weeks old	↓	Improvement of glucose and lipid metabolism; ↑ intestinal microbiota abundance and diversity.
Zhang et al., 2019 (⁶⁶66. Zhang C, Wu W, Xin X, Li X, Liu D. Extract of ice plant (Mesembryanthemum crystallinum) ameliorates hyperglycemia and modulates the gut microbiota composition in type 2 diabetic Goto-Kakizaki rats. Food Funct 2019; 10: 3252-3261, doi: 10.1039/C9FO00119K. https://doi.org/10.1039/C9FO00119K... )	Supplementation with Extract of Ice Plant (IPE)	8 weeks	17 weeks old	↓	Improved glycemic control, pancreatic islet morphology, beta-cell survival, insulin secretion and composition of intestinal microbiota; ↓ glycated serum proteins; ↓ HOMA-IR.
Zhao et al., 2019 (⁶⁷67. Zhao J, Li Y, Sun M, Xin L, Wang T, Wei L, et al. The Chinese herbal formula Shenzhu Tiaopi granule results in metabolic improvement in type 2 diabetic rats by modulating the gut microbiota. Evid Based Complement Alternat Med 2019; 2019: 6976394, doi: 10.1155/2019/6976394. https://doi.org/10.1155/2019/6976394... )	Supplementation with Chinese herbal formula Shenzhu Tiaopi Granule	8 weeks	17 weeks old	↓	↓ Total cholesterol; changes in microbiota by enrichment of Proteobacteria.
Zhao et al., 2020 (⁶⁸68. Zhao F, Liu Q, Cao J, Xu Y, Pei Z, Fan H, et al. A sea cucumber (Holothuria leucospilota) polysaccharide improves the gut microbiome to alleviate the symptoms of type 2 diabetes mellitus in Goto-Kakizaki rats. Food Chem Toxicol 2020; 135: 110886, doi: 10.1016/j.fct.2019.110886. https://doi.org/10.1016/j.fct.2019.11088... )	Supplementation with sea cucumber Holothuria leucospilota polysaccharide (HLP)	4 weeks	23 weeks old	↔	Improved glycemic control and lipid levels; ↓ serum insulin, adiponectin, and abnormal insulin signaling, and apoptosis-related molecules; ↑ serum leptin and GLP-1 and insulin signaling and anti-apoptotic genes; ↑ SCFA-producing bacteria and ↓ opportunistic pathogenic bacteria in GK feces; ↑ doses of HLP eliminated damage to the pancreas and colon of diabetic rats.
Péan et al., 2020 (²⁶26. Péan N, Le Lay A, Brial F, Wasserscheid J, Rouch C, Vincent M, et al. Dominant gut Prevotella copri in gastrectomised non-obese diabetic Goto-Kakizaki rats improves glucose homeostasis through enhanced FXR signalling. Diabetologia 2020; 63: 1223-1235, doi: 10.1007/s00125-020-05122-7. https://doi.org/10.1007/s00125-020-05122... )	Vertical sleeve gastrectomy (VSG) and transfer of the intestinal microbiota	13 weeks	29 weeks old	↔	Enrichment of Prevotella copri improved glucose and bile acid metabolism.
Yu et al., 2020 (⁶⁰60. Yu X, Wu Z, Song Z, Zhang H, Zhan J, Yu H, et al. Single-anastomosis duodenal jejunal bypass improve glucose metabolism by regulating gut microbiota and short-chain fatty acids in Goto-Kakisaki rats. Front Microbiol 2020; 11: 273, doi: 10.3389/fmicb.2020.00273. https://doi.org/10.3389/fmicb.2020.00273... )	Single-anastomosis duodenal jejunal bypass (DJB-sa)	8 weeks	21 weeks old	↔	Improved glycemic control; ↓ fasting serum insulin; ↑ GPL-1, SCFA receptors and SCFA-producing bacteria.
Tan et al., 2021 (⁶⁹69. Tan C, Zheng Z, Wan X, Cao J, Wei R, Duan J. The role of gut microbiota and amino metabolism in the effects of improvement of islet β-cell function after modified jejunoileal bypass. Sci Rep 2021; 11: 4809, doi: 10.1038/s41598-021-84355-x. https://doi.org/10.1038/s41598-021-84355... )	Modified jejunoileal bypass (SSJIBL)	6 weeks	14 weeks old	↓	Improved glycemic control. ↓ serum lipids, FFAs and liver injury markers; ↑ GLP-1, TNF-α, IL-6, insulin expression, and proliferation marker. ↑ Firmicutes and Proteobacteria and ↓ of Bacteroidetes in GK feces after surgery.
Zhao et al., 2021 (⁷⁰70. Zhao JD, Li Y, Sun M, Yu CJ, Li JY, Wang SH, et al. Effect of berberine on hyperglycaemia and gut microbiota composition in type 2 diabetic Goto-Kakizaki rats. World J Gastroenterol 2021; 27: 708-724, doi: 10.3748/wjg.v27.i8.708. https://doi.org/10.3748/wjg.v27.i8.708... )	Supplementation with berberine	8 weeks	15 weeks old	↔	↑ GLP-1 and ↓ HOMA-IR; improvement of pancreatic islet morphology.

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[1] Correspondence: G.M. Gimenes: <mandu.gabriela@gmail.com>