Effect Of Insulin Research Articles

Вторичные мессенджеры инсулина при синдроме поликистозных яичников и методы его патогенетической коррекции

The study of new mechanisms of insulin resistance (IR) formation is a prerequisite for the development of new pathogenetically-oriented therapies of polycystic ovary syndrome (PCOS) and the treatment of associated disorders of carbohydrate and fat metabolism. Important regulators of insulin signaling are its secondary messengers, namely myo-inositol (MI), D-chiro inositol (DCI), and α-lipoic acid (ALA), which mediate various effects of insulin. Consequently, MI induces cellular glucose uptake and enhances glycolysis, whereas DCI stimulates glycogenesis and regulates energy metabolism. The physiologic MI/DCI ratio for oocytes is crucial for oogenesis, steroidogenesis, and the regulation of the menstrual cycle. ALA provides insulinomimetic effects through the induction of glucose translocation into cells, antioxidant and anti-inflammatory effects on pancreatic cells, and the suppression of lipolysis and the reduction of triglyceride levels. A wealth of evidence from large-scale studies, meta-analyses, and systematic reviews has demonstrated the crucial role of MI, DCI, and ALA in the treatment of PCOS. A multitude of studies, including those conducted by the authors, have demonstrated that the administration of these substances results in a reduction in HOMA, levels of glucose, insulin, triglycerides, low-density lipoproteins, and body mass index. This, in turn, has been shown to restore ovulation and the menstrual cycle in women with PCOS, as well as to reduce the risk of cardiometabolic diseases, including diabetes and nonalcoholic fatty liver disease KEYWORDS: polycystic ovary syndrome, inositol, myo-inositol, D-chiro inositol, alpha-lipoic acid, insulin resistance, fat metabolism, nonalcoholic fatty liver disease FOR CITATION: Ivanov I.A., Tabeeva G.I., Smetnik A.A. Secondary messengers of insulin in polycystic ovary syndrome and its pathogenically- oriented treatment. Russian Journal of Woman and Child Health. 2024;7(2):135–143 (in Russ.). DOI: 10.32364/2618-8430-2024-7-2-8.

Effect of Oral Insulin on Early Combined Glucose and C‐Peptide Endpoints in Individuals at High‐Risk for Type 1 Diabetes

Effect of Oral Insulin on Early Combined Glucose and C‐Peptide Endpoints in Individuals at High‐Risk for Type 1 Diabetes

Comparative study between topical insulin, autologous serum, and honey-based eye drops as adjunctive treatment in resistant corneal ulcer

Background Resistant keratitis is a difficult situation faced every day in ophthalmology clinics. Resistance to healing may be attributed to many factors. Many adjunctive agents are widely used in a trial to accelerate healing and to prevent resistance to eliminate the chance of development of disabling complications. Purpose The aim of this study was to compare the effectiveness of topical insulin, autologous serum, and honey-based eye drops as adjunctive therapies in resistant corneal ulcers. Patients and methods This prospective study investigated 45 eyes of infected keratitis not responding to culture-based medical treatment for 2 weeks. The eyes were divided into three groups each of 15 eyes. The insulin group was treated with topical insulin drops, the serum group with autologous serum drops, and the honey group with honey-based drops. Culture-based medical treatment was also continued in the three groups till complete healing was achieved. The results of the three groups were compared regarding the time needed for healing and best-corrected visual acuity outcome. Results Best-corrected visual acuity improved by one or more lines in 11 (73.33%) cases in the insulin group, in 10 (66.67%) cases in the serum group, and in nine (60%) cases in the honey group, with no statistically significant difference (χ 2=1.525, P=0.822). Healing occurred in 14–28 days in 12 (80%) cases in the insulin group, in 13 (86.67%) cases in the serum group, and in 10 (66.67%) cases in the honey group, with no statistically significant difference (χ 2=1.8, P=0.407). The remaining cases in each group required amniotic membrane transplantation due to thinning. Conclusion The effects of topical insulin, autologous serum, and honey-based eye drops, when used as adjunctive methods added to the culture-based medical therapy in the management of resistant corneal ulcers, were comparable. Autologous serum gave slightly higher effect than topical insulin and honey-based eye drops but the difference was statistically insignificant.

A comparative study of the benefits of monotherapy rosiglitazone versus rosiglitazone with insulin in streptozotocin-induced diabetes in rats

Background: Diabetes is often associated with dyslipidemia, where plasma lipid and lipoprotein profile alterations increase the risk of coronary heart disease. Insulin resistance increases the risk of hyperinsulin and atherosclerosis, developing hypertension and diabetes. Patients with diabetes suffer from metabolic disorders in carbohydrates, fat, and proteins associated with hyperglycemia. Hence reducing insulin resistance is a therapeutic approach to treating diabetes. Aims and Objectives: The aim of the study was to evaluate the beneficial effects of monotherapy rosiglitazone, gemfibrozil, and insulin versus rosiglitazone, gemfibrozil, and insulin combination in streptozotocin-induced diabetes in rats. Materials and Methods: 42-Wistar rats of either sex were used in this study, except for the control group, streptozocin was used to induce diabetes. These rats were further allocated into five groups, each group consists of eight animals. Blood serum was used to estimate blood glucose and serum lipid levels were observed after a period of 6 weeks. Results were analyzed using SPSS software version 21.0. Results: Combination therapy of insulin + rosiglitazone + gemfibrozil showed a significant decrease in serum blood glucose, lipid levels in compared with vehicle and rosiglitazone groups. Conclusion: The results of our study demonstrated a more favorable lipid profile than the monotherapy regimen; adding gemfibrozil and insulin to rosiglitazone could help reverse the cardiovascular adverse events it causes.

ANTIOXIDANTS ENHANCE CHROMIUM (VI) MEDIATED TOXICITY IN NEUROSPORA CRASSA

Chromium can be found in the environment in two main valence states: hexavalent Cr (VI) and trivalent Cr (III). Reduction activation of carcinogenic Cr (VI) is required for the induction of DNA damage and mutations. There is a controversy over antioxidants’ role in Cr (VI) toxicity and cell death in mammalian systems. In the present study we compared the effect of antioxidants and insulin on Cr (VI) induced genotoxicity in wall-less mutant of Neurospora crassa (slime), which contains insulin receptor on its cell surface as a model system. Analysis by comet assay indicated Potassium dichromate (K2 Cr2 O7 ) induced DNA damage in slime cells, as increase in comet tail moment and the effect was dose dependent. Simultaneous addition of N-acetyl cysteine (NAC) & Sodium ascorbate (ASC) increased the extent of DNA damage whereas insulin decreased the extent of DNA damage induced by Cr (VI). The simultaneous exposure of antioxidants and insulin in presence of Cr (VI) showed enhanced cytotoxicity as observed by MTT assay. The results obtained suggest that N-acetyl cysteine and Sodium ascorbate reduce Cr (VI) to Cr (III) enhancing the levels of reactive oxygen species. Absence of protective role of insulin in presence of antioxidants indicate that a differential route may be adopted by the cells in response to metallic stress.

Analysis of current situation and influencing factors of cognitive dysfunction associated with type 2 diabetes and follow-up study on treatment effectiveness.

Many studies have explored the risk factors associated with cognitive impairment in patients with Type 2 diabetes mellitus (T2DM). However, research on determining the optimal threshold for these risk factors and comparative studies on the therapeutic effects of insulin and metformin is limited. This study aims to establish the optimal threshold for cognitive impairment risk factors in T2DM patients and compare the efficacy of insulin and metformin in treating mild cognitive impairment (MCI). A total of 308 patients with T2DM were included. The optimal threshold for cognitive impairment risk factors was determined using receiver operating characteristic curve and binary logistic regression models. MCI patients were divided into three groups: insulin, metformin, and insulin with metformin. The treatment effect was evaluated after a 6-month follow-up. The study identified several factors that influenced cognitive function in T2DM patients, including female gender, duration of diabetes >13.50 years, years of education >7.50 years, and serum sodium level > 141.90 mmol/L. Metformin and insulin with metformin showed superior therapeutic effects compared to insulin alone, but no difference was observed between metformin and combination therapy. Special attention should be given to female and those with diabetes duration >13.50 years, as well as to individuals with educational level ≤ 7.50 years and serum sodium concentration ≤ 141.90 mmol/L. Metformin and insulin with metformin effectively improve MCI in patients with T2DM and outperform insulin monotherapy. The efficacy of metformin and combination therapy was found to be comparable.

Oral Findings, Salivary Copper, Magnesium, and Leptin in Type II Diabetic Patients in Relation to Oral Candida Species.

Type 2 diabetes is a condition in which the body becomes resistant to the effects of insulin, leading to reduced insulin production in the pancreas. It has genetic- and family-related risk factors that cannot be changed, along with modifiable lifestyle factors. The precise genetic causes of type 2 diabetes are still unknown. However, individuals can potentially slow or stop the progression of the condition by making dietary adjustments and increasing physical activity levels. Material and Methods. Forty-five type II diabetic patients in the study included participants between 40 and 60 years old, with a minimum duration of one year, as well as 45 healthy control subjects who were matched in terms of age and sex, and had no underlying systemic diseases. Oral examination is done for the symptoms including burning sensation, candidiasis, and a reduction in the production of saliva. The rate of saliva flow (in milliliters per minute) was measured in samples of saliva that were not stimulated. The salivary trace elements and levels of adipocytokines were evaluated using colorimetric and Ethylenediaminetetraacetic acid (ELISA) testing. The quantification of Candida colony numbers, an enrichment and culture approach, was used to achieve a concentration of 100,000 colony-forming units per milliliter (CFU/ml). The ShowNovo WG1 halimeter was used to measure volatile sulfur compounds in breath. The salivary glucose oxidase assay was conducted using a colorimetric technique, while the determination of trace elements was also performed using a colorimetric assay method. The diabetic group exhibited a significant increase in the number of Candida spp colonies due to elevated levels of glucose in the saliva (p > 0.05). However, the variables being examined, such as body mass index (BMI), burning mouth syndrome (BMS), salivary flow rate (SFR), salivary leptin, salivary copper, and salivary magnesium, did not exhibit any significant variations in quantities between the diabetic and healthy groups (p > 0.05). The data collected in this research aid in the creation of a preventative program for oral fungal infections in individuals with type 2 diabetes. The program utilizes saliva and its constituents.

Insulin Secretion in Extended Mixed-Meal Tolerance Test in the Context of the Four Phases of Digestion

Background: A sequential response of insulin secretion is likely to follow the sequential pattern of digestion to optimize the effect of insulin and other counter regulatory peptides on the target tissues to maintain optimum insulin signaling pathway activation. Therefore, it is likely to relate insulin secretory response to the corresponding phase of digestion. Patients and methods: Plasma glucose, insulin and glucagon levels of three groups, each comprises of 10 persons. Group “N” for normal, group “P” for pre-diabetic and group “D” for type 2 diabetes individuals. Fluctuations in insulin secretion, in relation to changes of plasma glucose levels throughout the four phases of digestion will be traced, changes in glucagon levels will be also evaluated. Results: Early in the gastric-filling phase insulin was decreasing while glucose was rising, whereas, early in the gastric-emptying phase, insulin was rising while glucose was decreasing. Statistical significance of glucagon changes was higher than that of insulin between groups. Conclusion: Factors, which regulate insulin secretion during the gastric-filling phase, may differ than those during the gastric emptying-phase. Insulin/Glucagon ratio, is more contributed, than insulin alone, to the metabolic abnormalities associated with diabetes. It is more informative to consider insulin secretion in relation to the corresponding phase of digestion. Therefore, a four- phase cycle of insulin secretion may be suggested.

MODERN VIEWS ON THE PATHOGENESIS OF IMMUNE DYSFUNCTION AGAINST THE BACKGROUND OF THE METABOLIC SYNDROME IN ISCHEMIC HEART DISEASE

Introduction. Today, the pathology of the cardiovascular system is one of the most common and fatal diseases. Cardiovascular diseases are the cause of disability among the younger and younger population. Taking into account the frequency of cardiovascular diseases, the severity of the course and their lethality, the study of this topic remains one of the most urgent problems of medicine, in particular cardiology.
 The aim of the study. Consider modern views on the pathogenesis of coronary heart disease against the background of metabolic syndrome and the role of the immune system.
 Conclusions. Ischemic heart disease is the leading cause of mortality in Ukraine and the world. In recent years, there has been convincing evidence of a significant prevalence of cardiovascular disease in patients with metabolic syndrome. The presence of concomitant metabolic syndrome in patients with coronary heart disease worsens the course of the underlying disease and has an unfavorable prognosis, and even fatal cases.
 Therefore, the detection of an increase in the level of body mass index, dyslipidemia, hyperglycemia, arterial hypertension in a patient strengthens the effects of each other, that is, they have a synergistic effect, and in general, the risk of developing CHD becomes quite high.
 IL-6 is one of the cytokines released by both macrophages and adipocytes and its levels have been shown to be increased in insulin resistance and obesity. In fact, IL-6 is known to regulate fat and glucose metabolism, mediating insulin resistance through various complex mechanisms. This cytokine acts on various tissues, leading to the metabolic effects of obesity. In the liver, IL-6 increases the production of acute phase reactants, including CRP. Several studies have demonstrated that high CRP levels have the strongest correlation with cardiac events, T2DM, and MS. IL-6 also contributes to a prothrombotic state by increasing the level of fibrinogen, another acute phase reactant. In addition, IL-6 targets other tissues, such as endothelial cells, to promote the expression of vascular cell adhesion molecules, leading to vascular wall atherosclerosis, inflammation, and dysfunction.
 These data support the role of IL-6 in the development of insulin resistance, but do not support the hypothesis that IL-6 is involved in β-cell failure.
 IL-18 is a pro-inflammatory cytokine associated with insulin resistance and T2DM risk. IL-18 stimulates the production of gamma interferon (IFN-γ), which, in turn, is probably involved in the pathogenesis of atherosclerosis. IL-18 is a cytokine that is a predictor of metabolic syndrome.
 TNFα is another cytokine produced in adipose tissue, mainly from local macrophages, and its production also varies with adipose tissue mass and correlates with insulin resistance, both hallmarks of MS. TNFα exerts its pathogenic effects by disrupting insulin signaling in adipocytes and hepatocytes through serine phosphorylation and inactivation of insulin receptors and downstream signaling molecules, leading to decreased metabolic effects of insulin. TNFα also contributes to insulin resistance by inducing hepatic lipolysis.

Stepwise Discovery of Insulin Effects on Amino Acid and Protein Metabolism.

A clear effect of insulin deficiency and replacement on body/muscle mass was a landmark observation at the start of the insulin age. Since then, an enormous body of investigations has been produced on the pathophysiology of diabetes mellitus from a hormonal/metabolic point of view. Among them, the study of the effects of insulin on body growth and protein accretion occupies a central place and shows a stepwise, continuous, logical, and creative development. Using a metaphor, insulin may be viewed as a director orchestrating the music (i.e., the metabolic effects) played by the amino acids and proteins. As a hormone, insulin obviously does not provide either energy or substrates by itself. Rather, it tells cells how to produce and utilize them. Although the amino acids can be released and taken up by cells independently of insulin, the latter can powerfully modulate these movements. Insulin regulates (inhibits) protein degradation and, in some instances, stimulates protein synthesis. This review aims to provide a synthetic and historical view of the key steps taken from the discovery of insulin as an "anabolic hormone", to the in-depth analysis of its effects on amino acid metabolism and protein accretions, as well as of its interaction with nutrients.

Causal relationship between glycemic traits and bone mineral density in different age groups and skeletal sites: a Mendelian randomization analysis.

Previous research has confirmed that patients with type 2 diabetes mellitus tend to have higher bone mineral density (BMD), but it is unknown whether this pattern holds true for individuals without diabetes. This Mendelian randomization (MR) study aims to investigate the potential causal relationship between various glycemic trait (including fasting glucose, fasting insulin, 2-h postprandial glucose, and glycated hemoglobin) and BMD in non-diabetic individuals. The investigation focuses on different age groups (15-30, 30-45, 45-60, and 60 + years) and various skeletal sites (forearm, lumbar spine, and hip). We utilized genome-wide association study data from large population-based cohorts to identify robust instrumental variables for each glycemic traits parameter. Our primary analysis employed the inverse-variance weighted method, with sensitivity analyses conducted using MR-Egger, weighted median, MR-PRESSO, and multivariable MR methods to assess the robustness and potential horizontal pleiotropy of the study results. Fasting insulin showed a negative modulating relationship on both lumbar spine and forearm. However, these associations were only nominally significant. No significant causal association was observed between blood glucose traits and BMD across the different age groups. The direction of fasting insulin's causal effects on BMD showed inconsistency between genders, with potentially decreased BMD in women with high fasting insulin levels and an increasing trend in BMD in men. In the non-diabetic population, currently available evidence does not support a causal relationship between glycemic traits and BMD. However, further investigation is warranted considering the observed gender differences.

Study of age, sex and body mass index wise variation in C-peptide level among urban population of Northern part of Bihar

Background: Different factors regulate the insulin level in blood. Earlier C-peptide was considered as by product of insulin biosynthesis and its role in body seems to be negligible. C-peptide at low physiological concentrations mimics the effects of insulin. However, in the presence of elevated level of insulin concentrations concomitant raised level of C-peptide may blunt peripheral effects of insulin age. This study was carried out to verify the age, sex, and BMI wise variation in level of C-peptide among apparently healthy individual and its contribution in fine-tuning of the tissue’s metabolism under different physiological conditions. Methods: This is a prospective cross-sectional observational study. Estimation of serum c-peptide level was done by solid phase direct sandwich enzyme linked immunosorbent assay (ELISA) kit method. Glucose is estimated by Glucose oxidase peroxidase (GOD-POD) end point colorimetric method and HbA1C was estimated by ion exchange resin method (kit method). Result: Serum C-peptide level is significantly high in advance age and males in compared to younger age and females respectively. The mean level of serum C-peptide is higher in higher body mass index (BMI) group compared to lower, but this difference is statistically insignificant. Conclusions: In normal subjects, the level of C-peptide shows positive correlation with age and BMI. Males have higher level of C-peptide in comparison to females. Apart from these variation C-peptide contributes to different biological effects.

Mixed nut consumption improves brain insulin sensitivity: a randomized, single-blinded, controlled, crossover trial in older adults with overweight or obesity

BackgroundImproving brain insulin sensitivity, which can be assessed by measuring regional cerebral blood flow (CBF) responses to intranasal insulin, may prevent age-related metabolic and cognitive diseases. ObjectivesThis study aimed to investigate longer-term effects of mixed nuts on brain insulin sensitivity in older individuals with overweight/obesity. MethodsIn a randomized, single-blinded, controlled, crossover trial, 28 healthy adults (mean ± standard deviation: 65 ± 3 years; body mass index: 27.9 ± 2.3 kg/m2) received either daily 60-g mixed nuts (15 g of walnuts, pistachio, cashew, and hazelnuts) or no nuts (control) for 16 weeks, separated by an 8-week washout period. Throughout the study, participants were instructed to adhere to the Dutch food-based dietary guidelines. During follow-up, brain insulin action was assessed by quantifying acute effects of intranasal insulin on regional CBF using arterial spin labeling magnetic resonance imaging. Furthermore, effects on peripheral insulin sensitivity (oral glucose tolerance test), intrahepatic lipids, and cardiometabolic risk markers were assessed. ResultsBody weight and composition did not change. Compared with control, mixed nut consumption improved regional brain insulin action in 5 clusters located in the left (difference in CBF responses to intranasal insulin: −4.5 ± 4.7 mL/100 g/min; P < 0.001; −4.6 ± 4.8 mL/100 g/min; P < 0.001; and −4.3 ± 3.6 mL/100 g/min; P = 0.007) and right occipital lobes (−4.3 ± 5.6 mL/100 g/min; and −3.9 ± 4.9 mL/100 g/min; P = 0.028). A fifth cluster was part of the left frontal lobe (−5.0 ± 4.6 mL/100 g/min; P < 0.001). Peripheral insulin sensitivity was not affected. Intrahepatic lipid content (−0.7%-point; 95% CI: −1.3%-point to −0.1%-point; P = 0.027), serum low-density lipoprotein cholesterol concentration (−0.24 mmol/L; 95% CI: −0.44 to −0.04 mmol/L; P = 0.019), and systolic blood pressure (−5 mm Hg; 95% CI: −8 to −1 mm Hg; P = 0.006) were lower after the mixed nut intervention. ConclusionsLonger-term mixed nut consumption affected insulin action in brain regions involved in the modulation of metabolic and cognitive processes in older adults with overweight/obesity. Intrahepatic lipid content and different cardiometabolic risk markers also improved, but peripheral insulin sensitivity was not affected.This trial was registered at clinicaltrials.gov as NCT04210869.

A meta-analysis of metformin and insulin on maternal outcome and neonatal outcome in patients with gestational diabetes mellitus

Introduction The use of metformin for treating gestational diabetes mellitus (GDM) remains controversial because it can pass through the placenta. This meta-analysis aimed to compare the effects of metformin and insulin on maternal and neonatal outcomes in patients with GDM. Methods We conducted a comprehensive search of the PubMed, Embase, and Cochrane Library databases, focusing on randomized controlled trials (RCTs) that evaluated the impacts of metformin and insulin on both maternal and neonatal outcomes in patients with GDM. Results Twenty-four RCTs involving 4934 patients with GDM were included in this meta-analysis. Compared with insulin, metformin demonstrated a significant reduction in the risks of preeclampsia (RR 0.61, 95% CI 0.48 to 0.78, p < .0001), induction of labor (RR 0.90, 95% CI 0.82 to 0.98, p = .02), cesarean delivery (RR 0.91, 95% CI 0.85 to 0.98, p = .01), macrosomia (RR 0.67, 95% CI 0.53 to 0.83, p = .0004), neonatal intensive care unit (NICU) admission (RR 0.75, 95% CI 0.66 to 0.86, p < .0001), neonatal hypoglycemia (RR 0.55, 95% CI 0.48 to 0.63, p < .00001), and large for gestational age (LGA) (RR 0.80, 95% CI 0.68 to 0.94, p = .007). Conversely, metformin showed no significant impact on gestational hypertension (RR 0.84, 95% CI 0.67 to 1.06, p = .15), spontaneous vaginal delivery (RR 1.13, 95% CI 1.00 to 1.08, p = .05), emergency cesarean section (RR 0.94, 95% CI 0.77 to 1.16, p = .58), shoulder dystocia (RR 0.65, 95% CI 0.31 to 1.39, p = .27), premature birth (RR 0. 92, 95% CI 0.61 to 1.39, p = .69), polyhydramnios (RR 1.11, 95% CI 0.54 to 2.30, p = .77), birth trauma (RR 0.87, 95% CI 0.54 to 1.39, p = .56), 5-min Apgar score < 7 (RR 1.13, 95% CI 0.76 to 1.68, p = .55), small for gestational age (SGA) (RR 0.93, 95% CI 0.71 to 1.22, p = .62), respiratory distress syndrome (RDS) (RR 0.74, 95% CI 0.50 to 1.08, p = .11), jaundice (RR 1.09, 95% CI 0.95 to 1.25, p = .24) or birth defects (RR 0.80, 95% CI 0.37 to 1.74, p = .57). Conclusions The findings suggest that metformin can reduce the risk of certain maternal and neonatal outcomes compared with insulin therapy for GDM. However, long-term follow-up studies of patients with GDM taking metformin and their offspring are warranted to provide further evidence.

Insulin resistance in adipocytes: Novel insights into the pathophysiology of metabolic syndrome

Insulin resistance in all major target tissues is present in metabolic syndrome (MetS). The resistance in adipocytes is not well described and was presently examined. In this observational study on isolated abdominal white subcutaneous adipocytes from 419 adults, concentration-response effects of insulin on lipolysis inhibition (glycerol release) and lipogenesis stimulation (glucose conversion to total lipids) were determined. Insights into early and late insulin signaling events were obtained through the determination of insulin sensitivity (half maximum effective concentration) and responsiveness (maximum effect), respectively. In a subgroup of 132 subjects, we analyzed the subcutaneous adipose mRNA expression of genes in the canonical insulin signaling pathway using microarray. These results were validated using quantitative real-time polymerase chain reaction in 74 individuals. While the insulin responsiveness was similar in subjects with or without Mets, the sensitivity to insulin-mediated inhibition of lipolysis and stimulation of lipogenesis was ∼tenfold lower in subjects with MetS (p<0.0001). When age, sex, adipocyte volume, body mass index and body shape were considered, only the antilipolytic resistance was independently associated with MetS. The mRNA expression of several genes in the canonical insulin signaling pathway were altered in MetS (p<0.0006 or better) where the mRNA levels of insulin receptor substrate 2 associated with the antilipolytic effect (Rho=0.34; p=0.0016). The sensitivities of the antilipolytic and lipogenic effects of insulin are decreased in the MetS but only antilipolysis remains significant after multiple regression analysis. This resistance is localized at initial and receptor-near events in hormone signaling involving insulin receptor substrate 2.

Analysis of the management and therapeutic performance of diabetes mellitus employing special target.

Diabetes mellitus (DM) is a chronic metabolic condition characterized predominantly by hyperglycemia. The most common causes contributing to the pathophysiology of diabetes are insufficient insulin secretion, resistance to insulin's tissue-acting effects, or a combination of both. Over the last 30 years, the global prevalence of diabetes increased from 4% to 6.4%. If no better treatment or cure is found, this amount might climb to 430 million in the coming years. The major factors of the disease's deterioration include age, obesity, and a sedentary lifestyle. Finding new therapies to manage diabetes safely and effectively without jeopardizing patient compliance has always been essential. Among the medications available to manage DM on this journey are glucagon-like peptide-1 agonists, thiazolidinediones, sulphonyl urease, glinides, biguanides, and insulin-targeting receptors discovered more than 10 years ago. Despite the extensive preliminary studies, a few clinical observations suggest this process is still in its early stages. The present review focuses on targets that contribute to insulin regulation and may be employed as targets in treating diabetes since they may be more efficient and secure than current and traditional treatments.

Does insulin therapy affect all-cause mortality? machine learning complements propensity score analysis in a pharmacoepidemiologic study of adult diabetic females in Barranquilla, Colombia

Aims: To investigate all-cause mortality (ACM) attributable to insulin treated diabetes mellitus through propensity score (PS)-weighting with and without novel confounders identified by Random Survival Forest (a machine learning approach). Methods: Prospective clinic encounter data was obtained from 1517 females with Type 2 diabetes (mean age 63±12 years) from Barranquilla, Colombia (2003 – 2016, censored August 2017) for a median 10-year mortality follow-up. Risk variables of importance for ACM were identified on RSF screening. Survival was compared in retrospective cohorts, identified by baseline treatment with glucose-lowering therapy, and balanced for confounders through PS-weighting with and without RSF variables using multivariable Cox regression. Results: RSF screening identified new risk variables (e.g., recruitment year, parity, reproductive lifespan) for ACM in women receiving insulin. The unweighted risk estimate showed a nonsignificant increased risk for ACM [HR 1.32 (.9, 2), p=0.2] compared to noninsulin treated women. After balancing for risk covariates in the compared cohorts, PS showed no significant effect of insulin on all-cause mortality [HR 95% CI 0.83 (0.5, 1.4) p=0.5] whereas PS-weighted analyses incorporating RSF novel variables approached conservative ACM estimates [HR 95% CI 0.56 (0.3, 1.0) p=0.07)]. The estimated ACM risk from active smoking was also more conservative with RSF weighting. Conclusion: In this observational study, insulin treatment appeared to be a surrogate for higher-risk women with diabetes mellitus. RSF-augmented PS analysis showed that insulin treatment may potentially be associated with a survival advantage compared to non-insulin treatment in older female diabetics.

Congenital hyperinsulinism.

This clinical review will give doctors who work with children and neonates an introduction to the diagnosis and treatment of congenital hyperinsulinism, the most common cause of persistent neonatal hypoglycaemia. The condition is a rare monogenic disorder characterised by elevated insulin secretion and is a result of mutations in genes that regulate insulin secretion from pancreatic beta cells. The anabolic effect of insulin induces systemic glucose uptake and inhibits gluconeogenesis, glycogenolysis, ketogenesis and lipolysis. Low levels of glucose and ketone bodies in the blood are harmful to the central nervous system and can lead to brain damage or death. Early diagnosis and treatment of congenital hyperinsulinism are therefore crucial for a good prognosis.

Imaging the brain to assess brain insulin action

AbstractBackgroundEver since the brain was identified as an insulin‐sensitive organ, it was quickly appreciated that insulin action in the brain affects cognitive and metabolic processes [1]. Epidemiological evidence suggests a strong link between reduced peripheral insulin sensitivity and age‐related neurodegenerative processes, including Alzheimer’s disease (AD) [2].MethodCharacterization of brain insulin resistance in humans is challenging and relies on different neuroimaging methods in combination with insulin stimulation techniques. In my talk, I will focus on the administration of intranasal insulin, which has been established over the last decades to disentangle peripheral from brain insulin effects [1]. In combination with functional neuroimaging, I will show recent data on the quantification of brain insulin sensitivity non‐invasively in humans of different age and weight groups [3].ResultWe could show that intranasal insulin can affect region‐specific activity and functional connectivity of the human brain. These diverse central insulin responses largely depend on its action in the hypothalamus, amygdala, hippocampus, striatum and parts of the insula and prefrontal cortex and influences a variety of metabolic and cognitive processes [3]. Specifically, I will show that disrupted brain insulin action can result in increased accumulation of visceral fat and altered reward learning in persons at high risk to develop T2D [4], but also in healthy individuals after overconsumption of high caloric foods (unpublished). Moreover, I will show that the effect of intranasal insulin in the hippocampus decreases with age in women but not men and that brain insulin responsivity is affected by the menstrual cycle (unpublished). Moreover, just recently, we could link enhanced brain insulin action in the mesocorticolimbic circuitry with improved cognitive and metabolic functions [5].ConclusionAs brain insulin acts on striatal dopamine function and hippocampal plasticity, enhancing brain insulin action could lead to new treatment options in diabetes and aging‐associated diseases.

Effect of intra‐nasal insulin therapy on food intake among African American adults: the FIINAAL study

AbstractBackgroundIntranasal insulin is a promising treatment for cognitive decline in Alzheimer’s Disease (AD) and mild cognitive impairment (MCI). However, intranasal insulin has been shown to promote weight loss, leading to concerns about decreased appetite, decreased food intake, and unintentional weight loss as negative side effects among metabolic and ingestive behavior effects of intranasal insulin sprays among AD and MCI patients. But, side effects related to food intake and appetite are not well studied, particularly among African American adults who are under‐represented in AD research.Method39 middle‐aged, cognitively normal, community‐dwelling African American adults (Table 1) were enrolled in the Food Intake and Intranasal Insulin in African American Adults (FIINAAL) study assessing effects of intranasal insulin on acute food intake and appetite ratings. This double‐blind, placebo‐controlled, randomized crossover study compared a single intranasal dose of 10 IUs of Novologã insulin, delivered with the Kurveã device, to an intranasal placebo. Participants ate a eucaloric, macronutrient‐balanced lead‐in diet for three days prior to each dose. The dose was administered in the morning following an overnight fast. An ad libitum test lunch followed the dose and participants rated their appetite immediately before and after each dose, and after the meal. Mixed effects linear model t‐tests were used to compare differences in food intake and appetite ratings between insulin and placebo conditions.ResultThere were no significant differences in test lunch energy (calories) or macronutrient intake between insulin and placebo conditions. However, fullness ratings increased significantly more after receiving a dose of insulin than after a dose of placebo (Figure 1). In addition, desire to consume sweet and fatty foods decreased significantly more after insulin than after placebo (Figure 2).ConclusionIn middle aged African American adults, acute intranasal insulin administration was associated with a reduced desire to eat palatable foods and with increased feelings of fullness, but not with reduced food intake at a test meal. Because reduced appetite appears to be an acute side effect of intranasal insulin administration, future work should study whether chronic intranasal insulin administration results in reduced appetite and, consequently, reduced food intake and body weight over time.