The purinergic signalling and inflammation in the pathogenesis and progression of diabetes: key factors and therapeutic targets

Lima, André Campos de; Chaves, Lucas Macedo; Prestes, Samantha Nuncio; Mânica, Aline; Cardoso, Andréia Machado

doi:10.1007/s00011-022-01587-x

Cited by 5 publications

(3 citation statements)

References 113 publications

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“…Experimental models have shown that T exerts anti-inflammatory effects on several tissues [41][42][43] which represent a key element in the pathogenesis of insulin resistance and T2DM. 44 Pro-inflammatory adipocytokines, impaired insulin, and leptin signaling can contribute to hypothalamic gonadotropic suppression, at least partially, via effects on KNDy (kisspeptin/neurokinin B/dynorphin) neurons in the arcuate nucleus of the hypothalamus (see for review 29 ). In addition, at a cellular level, T is involved in the expression of the glucose carrier GLUT4, the insulin receptor, and the insulin receptor substrate 1, supporting insulin sensitivity proprieties.…”

Section: Discussionmentioning

confidence: 99%

“…The specific molecular mechanisms through which T can play a protective role in pre‐clinical and clinical diabetic conditions are far to be completely elucidated. Experimental models have shown that T exerts anti‐inflammatory effects on several tissues 41–43 which represent a key element in the pathogenesis of insulin resistance and T2DM 44 . Pro‐inflammatory adipocytokines, impaired insulin, and leptin signaling can contribute to hypothalamic gonadotropic suppression, at least partially, via effects on KNDy (kisspeptin/neurokinin B/dynorphin) neurons in the arcuate nucleus of the hypothalamus (see for review 29 ).…”

Section: Discussionmentioning

confidence: 99%

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Testosterone therapy in diabetes and pre‐diabetes

et al. 2022

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Background: Type 2 diabetes mellitus and pre-diabetes are associated with reduced circulating testosterone levels. However, the role of testosterone replacement therapy in these patients is still conflicting. Objectives:To summarize and critically analyze available data on the possible effect of testosterone administration in men with glucose abnormalities. Materials and methods:A comprehensive systematic review was performed. When available, meta-analytic data were preferred. To better analyze the relationship between testosterone and the pre-diabetes condition, a systematic analysis was performed and the data obtained with the latter search were used for a meta-analytic approach. Finally, clinical data derived from a consecutive series of 4682 patients seeking medical care for sexual dysfunction at the University of Florence were also considered.Results: Patients with impaired fasting glucose were characterized by a 3 nmol/L lower level of total testosterone when compared to controls. Similarly, impaired fasting glucose was associated with a 1.8-fold increased risk of hypogonadism, when compared to subjects with normal glucose levels. Waist circumference and body mass index resulted as being the best predictors of reduced total testosterone levels. Secondary hypogonadism was two times higher in subjects with impaired fasting glucose when compared to rates observed in the general population. Testosterone replacement therapy was able to improve body composition, insulin resistance, and glucose profile both in impaired fasting glucose and type 2 diabetes mellitus whereas its role on body weight, lipid profile, and sexual function was less evident.Discussion and conclusion: Weight loss and physical activities are able to improve both metabolic profile and testosterone levels. The combined approach of testosterone replacement therapy and lifestyle modifications could be suggested in symptomatic hypogonadal men to better motivate patients to perform physical activity which can eventually result in weight loss as well as metabolic profile and sexual function improvement. Whether or not these approaches can prevent the development of type 2 diabetes mellitus from pre-clinical conditions requires more studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Testosterone therapy in diabetes and pre‐diabetes

et al. 2022

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“…This was carried out in view of the lack of research on possible alterations in the roles of these receptors in the initial versus established phases of experimental diabetes. It is noteworthy that purinergic receptors were often proposed as a possible therapeutic target for several pathologies, including complications of diabetes mellitus [ 23 , 24 ]. Importantly, the studies included amperometric measurements of NO and H 2 O 2 signals in the renal medullary tissue in situ.…”

Section: Introductionmentioning

confidence: 99%

Nonselective and A2a-Selective Inhibition of Adenosine Receptors Modulates Renal Perfusion and Excretion Depending on the Duration of Streptozotocin-Induced Diabetes in Rats

et al. 2023

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Long-lasting hyperglycaemia may alter the role of adenosine-dependent receptors (P1R) in the control of kidney function. We investigated how P1R activity affects renal circulation and excretion in diabetic (DM) and normoglycaemic (NG) rats; the receptors’ interactions with bioavailable NO and H2O2 were also explored. The effects of adenosine deaminase (ADA, nonselective P1R inhibitor) and P1A2a-R-selective antagonist (CSC) were examined in anaesthetised rats, both after short-lasting (2-wks, DM-14) and established (8-wks, DM-60) streptozotocin-induced hyperglycaemia, and in normoglycaemic age-matched animals (NG-14, NG-60, respectively). The arterial blood pressure, perfusion of the whole kidney and its regions (cortex, outer-, and inner medulla), and renal excretion were determined, along with the in situ renal tissue NO and H2O2 signals (selective electrodes). The ADA treatment helped to assess the P1R-dependent difference in intrarenal baseline vascular tone (vasodilation in DM and vasoconstriction in NG rats), with the difference being more pronounced between DM-60 and NG-60 animals. The CSC treatment showed that in DM-60 rats, A2aR-dependent vasodilator tone was modified differently in individual kidney zones. Renal excretion studies after the ADA and CSC treatments showed that the balance of the opposing effects of A2aRs and other P1Rs on tubular transport, seen in the initial phase, was lost in established hyperglycaemia. Regardless of the duration of the diabetes, we observed a tonic effect of A2aR activity on NO bioavailability. Dissimilarly, the involvement of P1R in tissue production of H2O2, observed in normoglycaemia, decreased. Our functional study provides new information on the changing interaction of adenosine in the kidney, as well as its receptors and NO and H2O2, in the course of streptozotocin diabetes.

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