DESIGN: Preliminary assessment of serum levels of female hormones in women with or without T1DM. Then histological and immunological examinations were carried out on the pancreas, ovaries and uteri at different stages in non-obese diabetic (NOD) and Institute of Cancer Research (ICR) mice, as well as assessment of their fertility. A protein array was carried out to detect the changes in serum inflammatory cytokines. Furthermore, RNA-sequencing was used to identify the key abnormal genes/pathways in ovarian and uterine tissues of female NOD mice, which were further verified at the protein level.
RESULTS: Testosterone levels were significantly increased (P = 0.0036) in female mice with T1DM. Increasing age in female NOD mice was accompanied by obvious lymphocyte infiltration in the pancreatic islets. Moreover, the levels of serum inflammatory factors in NOD mice were sharply increased with increasing age. The fertility of female NOD mice declined markedly, and most were capable of conceiving only once. Furthermore, ovarian and uterine morphology and function were severely impaired in NOD female mice. Additionally, ovarian and uterine tissues revealed that the differentially expressed genes were primarily enriched in metabolism, cytokine-receptor interactions and chemokine signalling pathways.
CONCLUSION: T1DM exerts a substantial impairment on female reproductive health, leading to diminished fertility, potentially associated with immune disorders and alterations in energy metabolism.
METHOD: Multiple methods were used to determine molecular cognizance of AA in T2DM rats, when treated with different dosage levels. Histopathological and histomorphometry analysis was conducted using masson trichrome and H&E stains. While, protein and mRNA expressions of TLR-4/Wnt and insulin signaling were assessed using automated Western blotting (jess), immunohistochemistry, and RT-PCR.
RESULTS: Histopathological findings revealed that AA had reversed back the T2DM-induced apoptosis and necrosis caused to rats pancreas. Molecular findings exhibited prominent effects of AA in downregulating the elevated level of TLR-4, MyD88, NF-κB, p-JNK, and Wnt/β-catenin by blocking TLR-4/MyD88 and canonical Wnt signaling in diabetic pancreas, while IRS-1, PI3K, and pAkt were all upregulated by altering the NF-κB and β-catenin crosstalk during T2DM.
CONCLUSION: Overall results, indicate that AA has potential to develop as an effective therapeutic in the treatment of T2DM associated meta-inflammation. However, future preclinical research at multiple dose level in a long-term chronic T2DM disease model is warranted to understand its clinical relevance in cardiometabolic disease.
METHODS: F. deltoidea and vitexin was administrated orally to six-weeks STZ-induced diabetic rats over 8 weeks period. The glucose and insulin tolerances were assessed by intraperitoneal glucose (2 g/kg) tolerance test (IPGTT) and intraperitoneal insulin (0.65 U/kg) tolerance test (IPITT), respectively. Subsequently, insulin resistance was assessed by homeostasis assessment model of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and the insulin/triglyceride-derived McAuley index. The histological changes in the pancreas were then observed by hematoxylin-eosin (H&E) staining. Further, the pattern of fatty acid composition and infrared (IR) spectra of the serum and pancreas were monitored by gas chromatography (GC) method and Fourier Transform Infrared (FT-IR) spectroscopy.
RESULTS: F. deltoidea and vitexin increased pancreatic antioxidant enzymes and promoted islet regeneration. However, a significant increase in insulin secretion was observed only in rats treated with F. deltoidea. More importantly, reduction of fasting blood glucose is consistent with reduced FT-IR peaks at 1200-1000 cm-1.
CONCLUSIONS: These results accentuate that F. deltoidea and vitexin could be a potential agent to attenuate pancreatic oxidative damage and advocate their therapeutic potential for treating DM.
PURPOSE: The present study investigated the effects of oral treatment with M. pumilum var. alata (MPA) extracts on the estrogen receptor, metabolic characteristics and insulin signaling pathway in pancreas and liver of ovariectomised nicotidamide streptozotocin-induced diabetes in female rats.
MATERIALS AND METHODS: Ovariectomised diabetic (OVXS) Sprague-Dawley rats were orally administered with either aqueous leaf extract and ethanol (50%) stem-root extract of MPA (50 or 100 mg/kg) respectively for 28 days. Metabolic parameters were evaluated by measuring fasting blood glucose, serum insulin, oral glucose and insulin tolerance test. Distribution and expression level of insulin, oxidative stress and inflammatory marker in the pancreatic islets and liver were evaluated by immunohistochemistry and western blot, respectively.
RESULTS: Oral treatment with aqueous leaf and ethanol (50%) stem-root extracts of MPA (100 mg/kg) significantly reversed the elevated fasting blood glucose, impaired glucose and insulin tolerance. The protein expression of insulin, glucose transporter (GLUT-2 and GLUT-4) increased in the pancreatic islets and liver. Furthermore, marked improvement in the tissue morphology following treatment with MPA was observed. Similarly, the western blots analysis denotes improved insulin signaling in the liver and decreased reactive oxygen species producing enzymes, inflammatory and pro-apoptotic molecules with MPA treatment.
CONCLUSIONS: Taken together, this work demonstrate that 100 mg/kg of aqueous leaf extract and ethanol (50%) stem-root extract of MPA improves β-cell function and insulin signaling in postmenopausal diabetes through attenuation of oxidative stress and partially mediated by oestrogen receptor stimulation.
METHODS: Two parameters were measured (i) rate of glucose uptake by 3T3-L1 adipocyte cells in-vitro (ii) degree of pancreatic destruction in streptozotocin-nicotinamide induced male diabetic rats receiving M. pumilum aqueous extract (M.P) (250 and 500mg/kg/day) as reflected by levels of pancreatic oxidative stress, inflammation and apoptosis. In the meantime, phyto-chemical compounds in M.P were also identified by using LC-MS.
RESULTS: M.P was found able to enhance glucose uptake by 3T3-L1 adipocyte cells in-vitro while its administration to the male diabetic rats causes decreased in the fasting blood glucose (FBG), glycated haemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) levels but causes increased in insulin and high-density lipoprotein (HDL) levels, to near normal. Levels of oxidative stress in the pancreas as reflected by levels of lipid peroxidation product (LPO) decreased while levels of anti-oxidantive enzymes (SOD, CAT and GPx) in pancreas increased. Additionally, levels of inflammation as reflected by NF-κB p65, Ikkβ and TNF-α levels decreased while apoptosis levels as reflected by caspase-9 and Bax levels decreased. Anti-apoptosis marker, Bcl-2 levels in pancreas increased.
CONCLUSIONS: The ability of M.P to enhance glucose uptake and reduces pancreatic complications could account for its beneficial effects in treating DM.