Diabetic mouse models

The number of patients with lifestyle-related diseases, such as cardiovascular disease, diabetes mellitus, hypertension, atherosclerosis, and cancer, is increasing all over the world, and that of diabetics is increasing especially rapidly. Diabetic animal models have played a key role in elucidating the etiology of diabetes and developing anti-diabetic drugs. In this review, we overviewed characteristics of diabetic mouse models and pharmacological evaluation using the diabetic models.

Effect of phlorizin on metabolic abnormalities in Spontaneously Diabetic Torii (SDT) rats

The Spontaneously Diabetic Torii (SDT) rat is a novel model for nonobese type 2 diabetes. In this study we investigated the glycolipid metabolic changes with phlorizin-treatment, which inhibits intestinal glucose uptake and renal glucose reabsorption, in male SDT rats. Phlorizin (100 mg/kg, b.i.d., s.c.) was administered for 4 weeks to SDT rats from 20 to 24 weeks of age. As a result, phlorizin reduced the development of hyperglycemia and decreased the hemoglobin A1c (HbA1c) levels. In the liver, phlorizin increased mRNA levels of glucokinase, the enzymes related with the glycogen cascade and the proteins associated with lipid metabolism. In conclusion, chronic administration of phlorizin in SDT rats produced a good glycemic control and an improvement in liver function.

Female spontaneously diabetic Torii fatty rats develop nonalcoholic steatohepatitis-like hepatic lesions

AIM:To investigate the histological features of the liver in spontaneously diabetic Torii(SDT) fatty rats compared with age-matched Sprague-Dawley(SD) rats.METHODS:Female SDT Leprfa(SDT fatty) rats and age-matched SD rats were fed ad libitum. Body weight and biochemical parameters,such as serum glucose,triglyceride(TG),total cholesterol(TC),alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels as well as fatty acid and TG accumulation in the liver were evaluated at 8 wk of age in the nonfasting state and at 8-wk intervals from 8 to 40 wk of age. Histopathological examinations of the liver were performed using hematoxylin and eosin and Sirius Red staining as well as double staining for ED-1 and toluidine blue. The expression of genes involved in TG synthesis,inflammation,and fibrosis was examined in the liver.RESULTS:SDT fatty rats showed significantly increased body weight compared with SD rats. Serum glucose,TG,and TC levels were significantly higher in SDT fatty rats compared with SD rats. The serum AST and ALT levels in SDT fatty rats were significantly elevated at 8 wk of age compared with the levels in SD rats. Hepatic TG content was marked in SDT fatty rats from 8 to 32 wk of age. Histopathologically,severe hepatosteatosis accompanied by inflammation was observed at 8 wk of age,and fibrosis started to occur at 32 wk of age. Furthermore,Sirius Red and ED-1 staining were increased in the liver at 32 wk of age. Hepatic gene expression related to TG synthesis,inflammation and fibrosis tended to increase in SDT fatty rats compared with SD rats,and the gene expression related to TG secretion was decreased in SDT fatty rats compared with SD rats. CONCLUSION:Female SDT fatty rats have the potential to become an important animal model of nonalcoholic steatohepatitis with type 2 diabetes and obesity.

No replicated association of the c.-312A >G in<i>EDG</i>1 with marbling in Niigata population of Japanese Black beef cattle

Marbling, defined by the amount and the distribution of intramuscular fat and measured as beef marbling score (BMS), is an economically important trait of beef cattle in Japan. We recently reported that a single nucleotide polymorphism (SNP), namely, c.-312A > G, in the endothelial differentiation sphingolipid G-proteincoupled receptor, 1 (EDG1) gene was associated with the BMS level in the Japanese Black beef cattle population of Oita prefecture, with the G allele being associated with a high level of the BMS. Thus, the c.-312A > G SNP seems to be a candidate marker for marker-assisted selection. In this study, we investigated whether this association could be replicated in the Japanese Black beef cattle population of Niigata prefecture and analyzed the effect of the SNP genotypes on the carcass traits other than the BMS. No significant differences in the BMS level were detected among the genotypes of the c.-312A > G SNP in the Niigata Japanese Black beef cattle population. The SNP genotype had no significant effects on the carcass weight, rib eye area and rib thickness of the cattle population. These findings suggested that the association of the c.-312A > G SNP with the BMS level in the Japanese Black beef cattle population was not replicated in the Niigata population, and revealed no effects of the SNP genotype on the beef productivity in the Niigata population. Thus, we concluded that the c.-312A > G SNP is not useful for effective marker-assisted selection to increase meat quality and, additionally, meat productivity in Japanese Black beef cattle of Niigata prefecture.

Replicated association of the single nucleotide polymorphism in PNLIP with marbling in Niigata population of Japanese Black beef cattle

Marbling is regarded as an economically important trait of beef cattle inJapan, and measured as a beef marbling score (BMS). Our previous study reported an association between a single nucleotide polymorphism (SNP), rs4164 8172, in the pancreatic lipase (PNLIP) gene and the BMS level, using the Japanese Black beef cattle population of Oita prefecture. Further, we showed that the T allele at the rs41648172 SNP is associated with a high level of the BMS. Thus, we suggested that the rs41648172 SNP seems to be a candidate marker for marker-assisted selection. Our present study was designed to investigate whether this association could be replicated in other independent Japanese Black cattle population and analyze the effect of the SNP genotypes on the carcass traits other than the BMS. We detected the marginally significant effect of the genotypes of the rs41648172 SNP on the BMS level by using the Japanese Black beef cattle population of Niigata prefecture (P = 0.0919), and obtained the result of the T allele associated with an increase in the BMS level, consistent with our previous data. In addition, we showed no significant association of the SNP with the subcutaneous fat thickness, carcass weight, rib eye area, rib thickness and yield estimate in the Japanese Black beef cattle population ofNiigataprefecture. Thus, we concluded that the rs41648172 SNP was useful for effective marker-assisted selection to increase the BMS level in Japanese Black beef cattle, based on the replicated association of the rs41648172 SNP with the BMS level in the other independent Japanese Black beef cattle population and no effect of the SNP genotypes on the carcass traits other than BMS.

Non-Obese Type 2 Diabetic Rat Models-GK Rat and SDT Rat

The number of diabetic patients has recently been increasing all over the world together with lifestyle changes including sedentary life and high-calorie diet intake, and as a result the increase in these suffering from diabetes mellitus has become a global issue. Diabetic animal models play a key role in bettering our understanding of the pathophysiology of diabetes and in developing new therapies for the disease. Diabetes is classified into two types, type 1 and type 2, and type 2 diabetes is chiefly caused by a depletion of insulin secretion in the pancreas and insulin resistance in peripheral tissues. The Goto-Kakizaki (GK) rat and the Spontaneously Diabetic Torii (SDT) rat are genetic non-obese type 2 diabetic models, and the both rats are considered to be suitable models for investigating the etiology of the depletion of insulin secretion and impaired glucose tolerance. In this review, we overviewed the outline of pathophysiological features in GK rats and SDT rats, including biological parameters and pharmacological responses.

Allele Frequency Distribution of the NCAPG c.1326T>G SNP Associated with Growth-Related Traits in Niigata Population of Japanese Black Beef Cattle

Growth performance as well as marbling is the main breeding objectives in Japanese Black cattle, the major beef breed in Japan. A previous study has identified the c.1326T>G single nucleotide polymorphism (SNP) in the NCAPG (non-SMC condensin I complex, subunit G) gene that leads to the amino acid change p.Ile442Met in the NCAPG protein, which is a candidate causative variation for a bovine carcass weight (CWT) quantitative trait locus (QTL). In this study, we first confirmed the association of the c.1326T>G SNP with the growth-related traits, CWT, rib eye area (REA) and rib thickness (RT), and showed significant effect of the SNP genotypes on the marbling trait, beef marbling score (BMS), in the Japanese Black beef cattle population of the Niigata prefecture, with the G allele being associated with a favorable phenotype of these traits. Thus, we concluded that the c.1326T>G SNP is useful for effective marker-assisted selection to increase meat quality and meat productivity in Japanese Black beef cattle of the Niigata prefecture. Furthermore the frequency of the favorable G allele of the c.1326T>G SNP in the Niigata prefecture population was significantly lower than the frequency of this allele in Japanese Black cattle population of the Kagoshima prefecture. However, no statistically significant difference was detected between the allele frequencies estimated by maternal alleles in the half-sib progeny steers in the Niigata prefecture population and obtained in Japanese Black cattle population of the Kagoshima prefecture.

Allele Frequency Distribution in PNLIP Promoter SNP Is Different between High-Marbled and Low-Marbled Japanese Black Beef Cattle

Marbling defined by the amount and distribution of intramuscular fat is regarded as an economically important trait of beef cattle in Japan. The pancreatic lipase gene (PNLIP) is located within the genomic region of a bovine marbling quantitative trait locus. The rat homologue of PNLIP has been previously shown to be regarded as a possible candidate for the gene responsible for intramuscular fat content. These findings suggested that PNLIP was a positional and functional candidate for the marbling gene. In this study, we detected a single nucleotide polymorphism (SNP), g.37288470A > G, at 1917 bp upstream of the PNLIP transcription initiation site between Holstein steers and somatic nuclear-derived cloned steers from a Japanese Black sire with a very high estimated breeding value for marbling by sequencing analysis. Further, we found statistically significant difference in the allelic distribution of the SNP between 17 Japanese Black unrelated sires with extremely high predicted breeding values for marbling and 17 sires with extremely low ones (P = 0.0332). Our findings suggest that g.37288470A > G SNP in the promoter region of PNLIP might be associated with marbling by altering its gene expression, and be useful for effective marker-assisted selection to increase the levels of marbling in Japanese Black beef cattle.