RESUMO
Background: Urinary tract infection (UTI) is one of the most recurrent infections in the community and healthcare settings. Although many studies related with microbial sensitivity (MS) of uropathogens (UPs) to antibiotics have been done in Bangladesh, no conclusive study has compared antibiotic sensitivity (AS) to UPs in diabetic and non-diabetic patients. The aim of the study is to find out whether there is a difference in AS in common UPs between diabetic and non-diabetic UTI patients. Methods: A retrospective review was conducted on 833 patients. The data was collected from different diagnostic centers located within Dhaka city in Bangladesh, and the data was analyzed using convenient statistical tools. Results: We have studied a total of 833 UTI patients. Out of 833 patients, 664 were diabetic and 169 were non-diabetic patients respectively. Among the studied population, females were found to be more inclined to have UTIs as compared to males. E. coli was found to be the leading UPs in our study. Patients within the age of 20-34 were more vulnerable to UTI in both groups. Imipenem and meropenem showed 100% sensitivity against E. coli, Staphylococcus and Klebsiella in non-diabetic patients, while both antibiotics showed lower sensitivity to the same organisms in diabetic patients. Antibiotics like nitrofurantoin (p ≤ 0.0002), ceftazidime (p ≤ 0.0124) and ceftriaxone (p ≤ 0.0168) showed less sensitivity to E. coli in diabetic UTI patients as compared to non-diabetic UTI patients. Overall sensitivity patterns elucidated that all the studied antibiotics, except ciprofloxacin and levofloxacin, showed lower sensitivity against UPs in diabetic while compared to non-diabetic UTI patients (p= <0.05 to 0.0001). Conclusion: We found significant difference in microbial sensitivity in patients with diabetes compared to non-diabetic UTI patients. Diabetes changes the pathophysiological state of the uropathogens leading to the declining sensitivity of the antibiotics in diabetic patients with UTIs.
RESUMO
BACKGROUND: [6]-Gingerol, a major component of Zingiber officinale, was previously reported to ameliorate hyperglycemia in type 2 diabetic mice. Endocrine signaling is involved in insulin secretion and is perturbed in db/db Type-2 diabetic mice. [6]-Gingerol was reported to restore the disrupted endocrine signaling in rodents. In this current study on Leprdb/db diabetic mice, we investigated the involvement of endocrine pathway in the insulin secretagogue activity of [6]-Gingerol and the mechanism(s) through which [6]-Gingerol ameliorates hyperglycemia. METHODS: Leprdb/db type 2 diabetic mice were orally administered a daily dose of [6]-Gingerol (200 mg/kg) for 28 days. We measured the plasma levels of different endocrine hormones in fasting and fed conditions. GLP-1 levels were modulated using pharmacological approaches, and cAMP/PKA pathway for insulin secretion was assessed by qRT-PCR and ELISA in isolated pancreatic islets. Total skeletal muscle and its membrane fractions were used to measure glycogen synthase 1 level and Glut4 expression and protein levels. RESULTS: 4-weeks treatment of [6]-Gingerol dramatically increased glucose-stimulated insulin secretion and improved glucose tolerance. Plasma GLP-1 was found to be significantly elevated in the treated mice. Pharmacological intervention of GLP-1 levels regulated the effect of [6]-Gingerol on insulin secretion. Mechanistically, [6]-Gingerol treatment upregulated and activated cAMP, PKA, and CREB in the pancreatic islets, which are critical components of GLP-1-mediated insulin secretion pathway. [6]-Gingerol upregulated both Rab27a GTPase and its effector protein Slp4-a expression in isolated islets, which regulates the exocytosis of insulin-containing dense-core granules. [6]-Gingerol treatment improved skeletal glycogen storage by increased glycogen synthase 1 activity. Additionally, GLUT4 transporters were highly abundant in the membrane of the skeletal myocytes, which could be explained by the increased expression of Rab8 and Rab10 GTPases that are responsible for GLUT4 vesicle fusion to the membrane. CONCLUSIONS: Collectively, our study reports that GLP-1 mediates the insulinotropic activity of [6]-Gingerol, and [6]-Gingerol treatment facilitates glucose disposal in skeletal muscles through increased activity of glycogen synthase 1 and enhanced cell surface presentation of GLUT4 transporters.
