scholarly journals Bacillus toyonensis SAU-19 Ameliorates Hepatic Insulin Resistance in High-Fat Diet/Streptozocin-Induced Diabetic Mice

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4512
Author(s):  
Samuel Kumi Okyere ◽  
Lei Xie ◽  
Juan Wen ◽  
Yinan Ran ◽  
Zhihua Ren ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Antioxidant Status ◽  
Glycogen Synthesis ◽  
Hepatic Insulin Resistance ◽  
Histopathological Analysis ◽  
Bacillus Toyonensis

Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (T2DM). This study was performed to investigate the antidiabetic effect of Bacillus toyonensis SAU-19 and its possible mechanisms of action in mice with type 2 diabetes mellitus (T2DM). Thirty SPFKM mice were randomly assigned to three groups: control, diabetic model, and diabetes + Bacillus toyonensis SAU-19 group. After 35 days, blood was collected for biochemical analysis and liver tissue samples for histopathological analysis using H&E staining, qPCR, and ELISA. The results showed that the administration of B. toyonensis SAU-19 significantly improved the blood glucose, hepatic insulin resistance, and morphological changes of the liver characterized by significant improvement of dyslipidemia, glycogen synthesis, and antioxidant status (p < 0.05), indicating the strains’ ameliorating effects on hepatic insulin resistance in T2DM. In conclusion, the probiotic strain (B. toyonensis SAU-19) inhibits T2DM by reducing insulin resistance, improving antioxidant status, and downregulating genes related to glucose synthesis; hence, it may be used in treating diabetes and other metabolic disorders. This study provides the basis for further studies into the molecular mechanisms of B. toyonensis SAU-19 in treating T2DM.

ZFAND3 Overexpression in the Mouse Liver Improves Glucose Tolerance and Hepatic Insulin Resistance

2021 ◽  
Author(s):  
Kahori Shimizu ◽  
Yuya Ogiya ◽  
Kaede Yoshinaga ◽  
Hajime Kimura ◽  
Shotaro Michinaga ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Tolerance ◽  
Mouse Liver ◽  
Hepatic Insulin Resistance ◽  
Genome Wide Association Studies ◽  
Primary Mouse

AbstractGenome-wide association studies have identified more than 300 loci associated with type 2 diabetes mellitus; however, the mechanisms underlying their role in type 2 diabetes mellitus susceptibility remain largely unknown. Zinc finger AN1-type domain 3 (ZFAND3), known as testis-expressed sequence 27, is a type 2 diabetes mellitus-susceptibility gene. Limited information is available regarding the physiological role of ZFAND3 in vivo. This study aimed to investigate the association between ZFAND3 and type 2 diabetes mellitus. ZFAND3 was significantly upregulated in the liver of diabetic mice compared to wild-type mice. To overexpress ZFAND3, we generated a ZFAND3-expressing adenovirus (Ad) vector using an improved Ad vector exhibiting significantly lower hepatotoxicity (Ad-ZFAND3). Glucose tolerance was significantly improved in Ad-ZFAND3-treated mice compared to the control Ad-treated mice. ZFAND3 overexpression in the mouse liver also improved insulin resistance. Furthermore, gluconeogenic gene expression was significantly lower in primary mouse hepatocytes transduced with Ad-ZFAND3 than those transduced with the control Ad vector. The present results suggest that ZFAND3 improves glucose tolerance by improving insulin resistance and suppressing gluconeogenesis, serving as a potential novel therapeutic target for type 2 diabetes mellitus.

scholarly journals Diagnostic significance of serum PP4R1 and its predictive value for the development of chronic complications in patients with type 2 diabetes mellitus

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wenjing Li ◽  
Lanbo Peng ◽  
Chao Yang ◽  
Guangmin Chen
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Predictive Value ◽  
Diagnostic Value ◽  
Hepatic Insulin Resistance ◽  
Healthy Controls ◽  
Chronic Complications

Abstract Background Protein phosphatase 4 regulatory subunit 1 (PP4R1) is one of the regulatory subunits of PP4. It has been determined to be involved in the regulation of TNF-α-induced hepatic insulin resistance and gluconeogenesis. Considering the important role of PP4R1 in hepatic insulin resistance, the current study explored the expression and diagnostic value of PP4R1 in type 2 diabetes mellitus (T2DM) patients and further investigated its predictive value for the development of chronic complications. Method Hundred and five patients with T2DM and 97 healthy controls were collected. qRT-PCR was used for the measurement of serum PP4R1 mRNA level in both T2DM and control groups. The diagnostic value of PP4R1 in T2DM patients was evaluated using receiver operating characteristic (ROC) curve. Kaplan-Meier methods and Cox regression analysis were used to evaluate the predictive value of PP4R1 for the development of chronic complications in T2DM patients. Results PP4R1 was determined to be elevated in the serum of T2DM patients compared with healthy controls. Serum PP4R1 had the potential to distinguish T2DM patients from healthy controls with a sensitivity of 81.9% and specificity of 82.5%. Patients with high PP4R1 expression experienced more chronic complications events. The multivariate Cox analysis results suggested that serum PP4R1 expression was an independent factor for the occurrence of chronic complications for T2DM patients.  Conclusion PP4R1 is elevated in the serum of T2DM patients, had the potential to distinguish T2DM patients from healthy controls. PP4R1 serves as a promising biomarker for predicting the risk of future chronic complications in T2DM patients.

Abdominal fat distribution and peripheral and hepatic insulin resistance in type 2 diabetes mellitus

2002 ◽  
Vol 283 (6) ◽  
pp. E1135-E1143 ◽  
Author(s):  
Yoshinori Miyazaki ◽  
Leonard Glass ◽  
Curtis Triplitt ◽  
Estela Wajcberg ◽  
Lawrence J. Mandarino ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Type 2 Diabetes Mellitus ◽  
Subcutaneous Fat ◽  
Hepatic Insulin Resistance ◽  
Male And Female ◽  
Insulin Clamp

We examined the relationship between peripheral/hepatic insulin sensitivity and abdominal superficial/deep subcutaneous fat (SSF/DSF) and intra-abdominal visceral fat (VF) in patients with type 2 diabetes mellitus (T2DM). Sixty-two T2DM patients (36 males and 26 females, age = 55 ± 3 yr, body mass index = 30 ± 1 kg/m2) underwent a two-step euglycemic insulin clamp (40 and 160 mU · m−2 · min−1) with [3-3H]glucose. SSF, DSF, and VF areas were quantitated with magnetic resonance imaging at the L4–5 level. Basal endogenous glucose production (EGP), hepatic insulin resistance index (basal EGP × FPI), and total glucose disposal (TGD) during the first and second insulin clamp steps were similar in male and female subjects. VF (159 ± 9 vs. 143 ± 9 cm2) and DSF (199 ± 14 vs. 200 ± 15 cm2) were not different in male and female subjects. SSF (104 ± 8 vs. 223 ± 15 cm2) was greater ( P < 0.0001) in female vs. male subjects despite similar body mass index (31 ± 1 vs. 30 ± 1 kg/m2) and total body fat mass (31 ± 2 vs. 33 ± 2 kg). In male T2DM, TGD during the first insulin clamp step (1st TGD) correlated inversely with VF ( r = −0.45, P < 0.01), DSF ( r = −0.46, P < 0.01), and SSF ( r = −0.39, P < 0.05). In males, VF ( r = 0.37, P < 0.05), DSF ( r = 0.49, P < 0.01), and SSF ( r = 0.33, P < 0.05) were correlated positively with hepatic insulin resistance. In females, the first TGD ( r = −0.45, P < 0.05) and hepatic insulin resistance ( r = 0.49, P < 0.05) correlated with VF but not with DSF, SSF, or total subcutaneous fat area. We conclude that visceral adiposity is associated with both peripheral and hepatic insulin resistance, independent of gender, in T2DM. In male but not female T2DM, deep subcutaneous adipose tissue also is associated with peripheral and hepatic insulin resistance.

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