insulin resistance

摘要： Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures. 80 mg of S961 was stereotaxically injected into the lateral ventricle of the experimental group twice at 7 days apart, whereas buffer solution was injected to the sham control group. Blood samples, intraocular pressure, trabecular meshwork morphology, ciliary body markers, retinal and optic nerve integrity, and whole genome expression patterns were then evaluated. While neither blood glucose nor serum insulin level was significantly altered in the experimental or control group, we found that injection of S961 but not buffer solution significantly increased intraocular pressure at 14 and 24 days after first injection, along with reduced porosity and aquaporin 4 expression in the trabecular meshwork, and increased tumor necrosis factor α and aquaporin 4 expression in the ciliary body. In the retina, cell density and insulin receptor expression decreased in the retinal ganglion cell layer upon S961 injection. Fundus photography revealed peripapillary atrophy with vascular dysregulation in the experimental group. These retinal changes were accompanied by upregulation of pro-inflammatory and pro-apoptotic genes, downregulation of anti-inflammatory, anti-apoptotic, and neurotrophic genes, as well as dysregulation of genes involved in insulin signaling. Optic nerve histology indicated microglial activation and changes in the expression of glial fibrillary acidic protein, tumor necrosis factor α, and aquaporin 4. Molecular pathway architecture of the retina revealed the three most significant pathways involved being inflammation/cell stress, insulin signaling, and extracellular matrix regulation relevant to neurodegeneration. There was also a multimodal crosstalk between insulin signaling derangement and inflammation-related genes. Taken together, our results indicate that blocking insulin receptor signaling in the central nervous system can lead to trabecular meshwork and ciliary body dysfunction, intraocular pressure elevation, as well as inflammation, glial activation, and apoptosis in the retina and optic nerve. Given that central insulin resistance my lead to neurodegenerative phenotype in the visual system, targeting insulin signaling may hold promise for vision disorders involving the retina and optic nerve.

摘要： Through reading Chinese ancient book Huangdi Nejing,and summarizing and analyzing related literature,the basic pathogenesis of obesity have been found to be the stomach preponderance and spleen weakness,and the imbalance of ascending and descending.Banxia Xiexin Decoction not only has the functions of relieving heat to inhibit stomach intake,supplementing deficiency to assist spleen transport,regulate the ascending and descending,but also has the effects of improving insulin resistance and regulating glucolipid metabolism.Therefore,it is suggested that Banxia Xiexin Decoction can be used in the treatment of insulin resistant obesity,which provides ideas and methods for its treatment.

摘要： Background: Hypothyroidism has multiple etiologies and manifestation where accurate diagnosis and appropriate treatment is required and is in?uenced by coexisting medical conditions. This paper describes evidence-based clinical causes and indications. Objective: The objective is to review the clinical effect of hypothyroidism in different selected aspects and summarize the potential evidence about relationship between subclinical hypothyroidism with cardiovascular disease, diabetes mellitus, insulin resistance and mortality. Data Sources: A systematic review was conducted by searching English-language articles identified from 23 databases and search engines, yielding over 1000 documents. Study Selection: They are reports on the effects of hypothyroidism versus euthyroidism on obesity, insulin resistance, cardiovascular disease, coronary heart disease and mortality. Data Extraction: Data from research articles on hypothyroidism including subclinical hypothyroidism (SCH) and overt hypothyroidism, insulin resistance including diabetes mellitus and risk for coronary heart disease (CHD) including metabolic syndrome were independently assessed and summarized. Data Synthesis: Twelve of twenty-nine identified studies involved population-based cohorts, case controls and retrospective studies that included 4306 subjects. All 13 studies examined risks associated with subclinical hypothyroidism with type 2 diabetes mellitus (T2DM) and prevalence rates of SCH in T2DM patients ranged from 4.69% to 64.28% in the 12 included studies. Moreover, 4 studies out of the above 12 studies have revealed insulin resistance in the participants. Another population-based 12 studies have been carried out to assess hypothyroidism-related cardiac manifestation and according to the given data, average prevalence of CHD in hypothyroid participants is 25.20 (vary from 3.73 to 47.14) and it is 13.90 in euthyroid participants (vary from 1.17 to 38.49). Conclusions: Type 2 diabetes mellitus people are more likely to get subclinical hypothyroidism and subclinical hypothyroid population also shows several complications associated with type 2 diabetes mellitus. Besides, subclinical thyroid dysfunction might represent a risk factor for coronary artery disease and mortality.

摘要： The gut microbiota plays a key role in metabolic diseases.Gut-microbiota-derived metabolites are found in different dietary sources,including:Carbohydrate(acetate,propionate,butyrate,also known as short-chain fatty acids,as well as succinate);protein(hydrogen sulfide,indole,and phenylacetic acid);and lipids(resveratrol-,ferulic acid-,linoleic acid-,catechin-and berry-derived metabolites).Insulin resistance,which is a global pandemic metabolic disease that progresses to type 2 diabetes mellitus,can be directly targeted by these metabolites.Gutmicrobiota-derived metabolites have broad effects locally and in distinct organs,in particular skeletal muscle,adipose tissue,and liver.These metabolites can modulate glucose metabolism,including the increase in glucose uptake and lipid oxidation in skeletal muscle,and decrease in lipogenesis and gluconeogenesis associated with lipid oxidation in the liver through activation of phosphatidylinositol 3-kinase-serine/threonine-protein kinase B and AMP-activated protein kinase.In adipose tissue,gut-microbiota-derived metabolites stimulate adipogenesis and thermogenesis,inhibit lipolysis,and attenuate inflammation.Importantly,an increase in energy expenditure and fat oxidation occurs in the whole body.Therefore,the therapeutic potential of current pharmacological and non-pharmacological approaches used to treat diabetes mellitus can be tested to target specific metabolites derived from intestinal bacteria,which may ultimately ameliorate the hyperglycemic burden.

摘要： Stress hyperglycemia is a strong neuroendocrine reaction in the hypothalamic pituitary adrenal cortex under severe infection,trauma,burns,hemorrhage,surgery and other harmful stimulated,resulting in increased secretion of counter-regulatory hormones.These hormones promoted the production of sugar and cause glucose metabolism disorders with cytokines and insulin resistance.In this condition,the production of sugar exceeds the utilization of sugar by the tissues,which eventually leads to an increase in blood glucose levels in plasma.In the intensive care unit,stress hyperglycemia is very common and can occur in patients with or without diabetes.The incidence is as high as 96%,and it is an independent factor in the death of critically ill patients.Hyperglycemia not only prolongs the hospitalization time,mechanical ventilation time and increased the incidence of serious infections in critically ill patients,but can also lead to the occurrence of type 2 diabetes.Therefore,it is very important to learn the pathological mechanism of stress hyperglycemia,the harm of hyperglycemia and blood sugar management.

摘要： Metabolically healthy obese(MHO)individuals are reported to have a lower risk of developing cardiovascular diseases in comparison with individuals with metabolic syndrome.However,the association between MHO and type 2 diabetes(T2DM)is still controversial.Some studies indicated that MHO is a favorable phenotype for T2DM,but more studies showed that MHO individuals have an increased risk of developing T2DM compared with metabolically healthy normalweight individuals,especially among those who would acquire metabolically unhealthy obesity.This has been supported by finding insulin resistance and lowgrade inflammatory responses in MHO individuals with a tendency for impaired beta-cell dysfunction.Studies also showed that liver fat accumulation increased the risk of incidence of T2DM in MHO.Here,we reviewed current literature on the relationship between MHO and T2DM,discussed the determinants for the development of diabetes in MHO,and summarized the measures for the prevention of T2DM in MHO.

摘要： Polycystic ovary syndrome(PCOS)often coexists with a wide spectrum of dysglycemic conditions,ranging from impaired glucose tolerance to type 2 diabetes mellitus(T2D),which occur to a greater extent compared to healthy body mass index-matched women.This concurrence of disorders is mainly attributed to common pathogenetic pathways linking the two entities,such as insulin resistance.However,due to methodological flaws in the available studies and the multifaceted nature of the syndrome,there has been substantial controversy as to the exact association between T2D and PCOS which has not yet been elucidated.The aim of this review is to present the best available evidence regarding the epidemiology of dysglycemia in PCOS,the unique pathophysiological mechanisms underlying the progression of dysglycemia,the most appropriate methods for assessing glycemic status and the risk factors for T2D development in this population,as well as T2D risk after transition to menopause.Proposals for application of a holistic approach to enable optimal management of T2D risk in PCOS are also provided.Specifically,adoption of a healthy lifestyle with adherence to improved dietary patterns,such the Mediterranean diet,avoidance of consumption of endocrine-disrupting foods and beverages,regular exercise,and the effect of certain medications,such as metformin and glucagon-like peptide 1 receptor agonists,are discussed.Furthermore,the maintenance of a healthy weight is highlighted as a key factor in achievement of a significant reduction of T2D risk in women with PCOS.

摘要： BACKGROUND Insulin resistance(IR)and impaired energy expenditure(IEE)are irreparable metabolic comorbidities in schizophrenia.Although mechanism(s)underlying IR and IEE remains unclear,leptin and fatty acid signaling,which has profound influence on insulin secretion/sensitivity,glucose metabolism and energy expenditure,could be disrupted.However,no association of plasma leptin with erythrocyte membrane fatty acids,body mass index(BMI),and psychotic symptoms in the same cohort of untreated patients with first-episode psychosis(FEP)or medicated patients with chronic schizophrenia(CSZ)is presented before.These studies are crucial for deciphering the role of leptin and fatty acids in the development of IR and IEE in schizophrenia.AIM To determine the association between plasma leptin,erythrocyte membrane fatty acids,particularly,saturated fatty acids(SFAs),BMI and psychotic symptoms in patients with FEP and CSZ.METHODS In this study,twenty-two drug naive patients with FEP,twenty-one CSZ patients treated with atypical antipsychotic drugs,and fourteen healthy control(CNT)subjects were analyzed.Plasma leptin was measured using sandwich mode enzyme-linked immunosorbent assay.Erythrocyte membrane SFAs were measured using ultrathin capillary gas chromatography.BMI was calculated by using the formula:weight(kg)/height(m^(2)).Psychiatric symptoms were evaluated at baseline using brief psychiatric rating scale(BPRS),and positive and negative syndrome scale(PANSS).The total BPRS scores,positive and negative symptom scores(PANSS-PSS and PANSS-NSS,respectively)were recorded.Pearson correlation coefficient(r)analyses were performed to find the nature and strength of association between plasma leptin,PANSS scores,BMI and SFAs,particularly,palmitic acid(PA).RESULTS In patients with FEP,plasma leptin not BMI was significantly lower(P=0.034),whereas,erythrocyte membrane SFAs were significantly higher(P<0.005)compared to the CNT subjects.Further,plasma leptin showed negative correlation with erythrocyte membrane SFAs-PA(r=-0.4972,P=0.001),PANSS-PSS(r=-0.4034,P=0.028),and PANSS-NSS(r=-0.3487,P=0.048).However,erythrocyte membrane SFAs-PA showed positive correlation with PANSS-PSS(r=0.5844,P=0.0034)and PANSS-NSS(r=0.5380,P=0.008).In CSZ patients,plasma leptin,BMI,and erythrocyte membrane SFAs,all were significantly higher(P<0.05)compared to the CNT subjects.Plasma leptin showed positive correlation with BMI(r=0.312,P=0.032)but not with PANSS scores or erythrocyte membrane SFAs-PA.However,erythrocyte membrane SFAs-PA showed positive correlation with PANSS-NSS only(r=0.4729,P=0.031).Similar changes in the plasma leptin and erythrocyte membrane SFAs have also been reported in individuals at ultrahigh risk of developing psychosis;therefore,the above findings suggest that leptin-fatty acid biosynthesis could be disrupted before the onset of psychosis in schizophrenia.CONCLUSION Disrupted leptin-fatty acid biosynthesis/signaling could be an early manifestation of metabolic comorbidities in schizophrenia.Large-scale studies are warranted to validate the above findings.

摘要： BACKGROUND An increased risk of insulin resistance(IR)has been identified in rheumatoid arthritis(RA),a chronic inflammatory disorder with elevated levels of pathogenic cytokines.Biologics targeting proinflammatory cytokines can control the disease and improve insulin sensitivity in RA.Although Janus kinase(JAK)signaling can regulate cytokine receptors and participate in RA pathogenesis,it remains to be elucidated whether there is a reduction of IR in such patients under JAK inhibitor(JAKi)therapy.AIM To study the effect of JAKi treatment on the reduction of IR in RA patients with active disease.METHODS A retrospective study was carried out from April 1,2017 to March 31,2021 in a population of non-diabetic patients with active RA who were undergoing tofacitinib(TOF)therapy with 5 mg twice-daily immediate-release formulation.RESULTS Fifty-six RA patients,aged 30 years to 75 years(mean±SD:52.3±11.1)with disease activity score 28 values ranging from 4.54 to 7.37(5.82±0.74),were classified into high-IR(>2.0)and low-IR(≤2.0)groups based on their baseline homeostatic model assessment(HOMA)-IR levels.They had no previous exposure to JAKi,and received TOF therapy for no less than 6 mo.In 30 patients who were naïve to biologics,after a 24-week therapeutic period,the high-IR group showed reduced HOMA-IR levels (3.331 ± 1.036 vs 2.292 ± 0.707, P < 0.001). In another 26patients who were exposed to tumor necrosis factor-α or interleukin-6 blockers, the high-IR group,despite having achieved a decrease but with lower magnitude than in naïve patients, showedreduced HOMA-IR levels (2.924 ± 0.790 vs 2.545 ± 1.080, P = 0.018).CONCLUSIONIn this retrospective study, reduced IR was achieved in non-diabetic active RA patients following24 wk of TOF therapy.

摘要： The purpose of this scoping review is to create a single narrative that describes the impact of smoking cessation on metabolic parameters in people with diabetes.It is generally well accepted that smoking enhances the harmful effects of elevated blood glucose levels,accelerating the vascular damage seen in patients with diabetes.Smoking cessation has clear benefits in terms of reducing cardiovascular morbidity and mortality.However,there is less evidence for the impact of smoking cessation on other diabetes-related complications.Studies in people with diabetes have shown improvement as well as temporary deterioration in glycemic control after ceasing smoking.Only a few studies have described the effect of quitting smoking on insulin resistance and lipid parameters,however,their results have been inconclusive.In this situation,healthcare professionals should not assume that cessation of smoking will improve metabolic parameters in patients with diabetes.It seems they should, first of all, emphasize the prevention of weight gain that may be associatedwith quitting smoking. The lack of data regarding the metabolic effects of smoking and smokingcessation in diabetes is very disappointing and this area needs to be addressed.