Development of the Diabetic Kidney Disease Mouse Model Culturing Embryos in α-Minimum Essential Medium In Vitro, and Feeding Barley Diet Attenuated the Pathology

Abstract

Diabetic kidney disease (DKD) is a critical complication associated with diabetes; however, there are only a few animal models that can be used to explore its pathogenesis. In the present study, we established a mouse model of DKD using a technique based on the Developmental Origins of Health and Disease theory, i.e., by manipulating the embryonic environment, and investigated whether a dietary intervention could ameliorate the model’s pathology. Two-cell embryos were cultured in vitro in α-minimum essential medium (MEM; MEM mice) or in standard potassium simplex-optimized medium (KSOM) as controls (KSOM mice) for 48 h, and the embryos were reintroduced into the mothers. The MEM and KSOM mice born were fed a high-fat, high-sugar diet for 58 days after they were 8 weeks old. Subsequently, half of the MEM mice and all KSOM mice were fed a diet containing rice powder (control diet), and the remaining MEM mice were fed a diet containing barley powder (barley diet) for 10 weeks. Glomerulosclerosis and pancreatic exhaustion were observed in MEM mice, but not in control KSOM mice. Renal arteriolar changes, including intimal thickening and increase in the rate of hyalinosis, were more pronounced in MEM mice fed a control diet than in KSOM mice. Immunostaining showed the higher expression of transforming growth factor beta (TGFB) in the proximal/distal renal tubules of MEM mice fed a control diet than in those of KSOM mice. Pathologies, such as glomerulosclerosis, renal arteriolar changes, and higher TGFB expression, were ameliorated by barley diet intake in MEM mice. These findings suggested that the MEM mouse is an effective DKD animal model that shows glomerulosclerosis and renal arteriolar changes, and barley intake can improve these pathologies in MEM mice.

Actional Mechanism of Functional Ingredients in Beer and Barley for Human Health

“…Zeng et al [1] summarized the health effects of 22 chronic diseases of prevention and treatment, including antidiabetes, antiobesity, anticancer, antioxidants, improve gastrointestinal [49], antiinflammation, lower blood pressure, hepatoprotection, immunomodulation, alleviates atopic dermatitis, prevent cardiovascular diseases, hyperlipidemia, antiaging, cardioprotection, antifatigue, optimize cholesterol, improve bowel health, metabolic syndrome, prevent heart disease, reduce chronic kidney disease [50], accelerate wound healing, decrease stroke and cholelithiasis activities. Barley and adlay are the largest functional food with the use of 110 kinds of homologous substances in China, both barley grasses and grains can prevent and control more than 22 chronic diseases in humans or animals, due to molecular mechanism of barley grass (GABA, flavonoids, SOD, K-Ca, vitamins, and tryptophan) and grains (β-glucans, polyphenols, arabinoxylan, phytosterols, tocols, and resistant starch), especially support that human has only one cell disease theory, which provides a reference for the development of human functional food and animal husbandry production of functional feed [1,51].…”

Type 2 Diabetes Mellitus: Pathogenic Features and Experimental Models in Rodents

“…Polygenic models, namely KK and KK AY mice, OLETF rats, NZO mice, etc., are characterized by obesity-induced hyperglycemia, severe hyperinsulinemia, IR in both muscle and adipose tissue, and pronounced changes in the pancreatic islets: from hypertrophy and degranulation to fibrosis and their replacement by the connective tissue [ 67 , 68 , 69 , 70 ]. A number of works focused on the elimination of T2DM symptoms, analysis of the relationship between obesity and glucose homeostasis, as well as diabetic complications, have been done using polygenic models [ 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ].…”

From lessons on the long‐term effects of the preimplantation environment on later health to a “modified ART‐DOHaD” animal model

“…26,80 These results imply that the "MEM mouse" can be used as a novel animal model for human diabetes. [14][15][16] Although the underlying mechanisms induced by αMEM medium remain unknown, unlike KSOM-AA, this αMEM medium has no protein such as bovine serum albumin (BSA) while containing vitamins such as folic acid (Table 1). Considering that BSA in culture media plays an important role beyond a source of amino acids, 81 its absence may contribute to inducing the phenotype.…”

“…Recently, we have reported that mice derived from embryos treated with just αMEM medium, which is commonly used for mammalian cell culture, over 48 h, so‐called the “MEM mouse” exhibit increased weight with severe type 2 diabetes‐related phenotypes such as postprandial hyperglycemia, high inflammation gene expression, non‐alcoholic fatty liver disease, DKD, diabetic steatohepatitis, which are not observed in mice derived from embryos cultured in KSOM‐AA (mKSOM) medium, a KSOM medium supplemented with amino acids (Figure 3). 26,80 These results imply that the “MEM mouse” can be used as a novel animal model for human diabetes 14–16 . Although the underlying mechanisms induced by αMEM medium remain unknown, unlike KSOM‐AA, this αMEM medium has no protein such as bovine serum albumin (BSA) while containing vitamins such as folic acid (Table 1).…”

“…In this review, we first focus on the outcomes of IVC on subsequent development and phenotypes mainly in the mouse. Second, we introduce a new unique type 2 diabetes model mouse, the “MEM mouse,” which presents complications that include steatohepatitis, glomerulosclerosis, and arteriolosclerosis in the kidney as diabetic kidney disease (DKD), simply by exposure to alpha minimum essential medium (αMEM) for 48 h from the two‐cell embryo stage 14–16 …”