Search

Liraglutide, a glucagon-like peptide-1 receptor agonist, has been shown to regulate blood sugar and control body weight, but its ability to treat obesity-related nephropathy has been poorly studied. Therefore, this study was designed to observe the characteristics and potential mechanism of liraglutide against obesity-related kidney disease. Thirty-six C57BL/6J male mice were randomly divided into six groups (n = 6 per group). Obesity-related nephropathy was induced in mice by continuous feeding of high-fat diet (HFD) for 12 weeks. After 12 weeks, liraglutide (0.6 mg/kg) and AMP-activated protein kinase (AMPK) agonists bortezomib (200 μg/kg) were injected for 12 weeks, respectively. Enzyme-linked immunosorbent assay was employed to detect the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine in serum, as well as urinary protein in urine. Besides, hematoxylin–eosin staining and periodic acid-Schiff staining were used to observe the pathological changes of kidney tissue; immunohistochemistry, western blot, and real-time quantitative PCR to assess the calmodulin-dependent protein kinase kinase beta (CaMKKβ)/AMPK signaling pathway activation. Liraglutide significantly reduced serum lipid loading, improved kidney function, and relieved kidney histopathological damage and glycogen deposition in the mouse model of obesity-related kidney disease induced by HFD. In addition, liraglutide also significantly inhibited the CaMKKβ/AMPK signaling pathway in kidney tissue of HFD-induced mice. However, bortezomib partially reversed the therapeutic effect of liraglutide on HDF-induced nephropathy in mice. Liraglutide has a therapeutic effect on obesity-related kidney disease, and such an effect may be achieved by inhibiting the CaMKKβ/AMPK signaling pathway in kidney tissue. [ABSTRACT FROM AUTHOR]

Objective To explore the association among the management of diet and sport, glucose metabolism, bone metabolism, and bone mineral density (BMD) in postmenopausal women with type 2 diabetes mellitus (T2DM) and osteoporosis (OP). Methods A total of 562 postmenopausal women with T2DM and OP were selected and divided into two groups; the manage group (n = 278), and the control group (n = 284). Subjects in the 2 groups were given strict management and general management, respectively. All the patients took oral medication of glucose-lowering drugs with 600mg/d Caltrate D and 0. 25 ug/d calcitriol, simultaneously. At the beginning, the 24th week, and the 48th week of the treatment, the glucose metabolism indexes such as glycosylated hemoglobin Ale (HbAlc) and fasting plasma glucose (FPG), and the bone metabolism indexes such as vitamin D3 (VitD3), bone alkaline phosphatase (BALP), tartrateresistant acid phosphatase-5b (TRAP-5b), and serum osteocalcin (OC) were detected. BMD of different parts were measured using dual-energy X-ray absorptiometry, in order to explore the changes of each index after strict management. Results At the 24th week, HbAlC in the manage group decreased significantly compared to that in the control group, while at the 48' week, the result was even more significant. HbAlC in the manage group was 8. 16 ± 1. 50%, 7. 10 ± 1. 60%, and 6. 01 ± 1. 59% at the 0, the 24th, and the 48th week, respectively; and HbAlC in the control group was 8. 46 ± 1. 65%, 8. 16 ± 1. 03%, and 8. 21 ± 1. 02%, respectively. The decrease of HbAlC was observed in both manage group and control group, and was much more obvious in the manage group, and the difference between groups was significant (P < 0. 01). Meanwhile TRAP-5b in the manage group decreased obviously compared to that in the control group, while BALP, VitD3, and OC increased significantly (P < 0. 01). After 24th week treatment, BMD of the lumbar vertebrae and the femoral neck in the manage group increased gradually, while in the control group BMD showed a decreasing tendency. At the 48th week, BMD in 2 groups showed significant difference (P < 0. 01). Conclusion According to the specific condition in T2DM patients with OP, on the basis of original drug treatment, the management of strict diet control and appropriate individual exercise can effectively control the blood sugar, reduce bone loss, and increase BMD. [ABSTRACT FROM AUTHOR]