Effect Of Insulin Research Articles

(Pro)renin receptor and insulin signalling regulate cell proliferation in MCF-7 breast cancer cells.

(Pro)renin receptor [(P)RR] is related to both the renin-angiotensin system and V-ATPase with various functions including stimulation of cell proliferation. (P)RR is implicated in the pathophysiology of diabetes mellitus and cancer. Hyperinsulinemia is observed in obesity-related breast cancer. However, the relationship between (P)RR and insulin has not been clarified. We have therefore studied the effect of insulin on (P)RR expression, cell viability and AKT phosphorylation under the conditions with and without (P)RR knockdown. Effects of insulin were studied in a human breast cancer cell line, MCF-7. Cell proliferation assay was performed by WST-8 assay. (P)RR expression was suppressed by (P)RR-specific siRNAs. The treated cells were analysed by western blotting and reverse transcriptase-quantitative polymerase chain reaction analysis. Insulin stimulated proliferation of MCF-7 cells and increased (P)RR protein expression, but not (P)RR mRNA levels. Moreover, autophagy flux was suppressed by insulin. Suppression of (P)RR expression reduced cell number of MCF-7 cells and AKT phosphorylation significantly in both the presence and the absence of insulin, indicating that (P)RR is important for cell viability and AKT phosphorylation. In conclusion, insulin upregulates the level of (P)RR protein, which is important for cell viability, proliferation, AKT phosphorylation and autophagy in breast cancer cells.

ETIOPATHOGENESIS OF THYROID DISEASE AND ASSOCIATION WITH METABOLIC SYNDROME

In clinical practice, patients with metabolic syndrome and thyroid disease are often referred. It is noteworthy that based on the results of various population studies, there has been an increase in both thyroid disease and the incidence of signs of metabolic syndrome in adults. Therefore, there has been a dramatic increase in interest in the study of possible associations between these two pathological conditions. Based on the results of various papers, the close relationship between these two pathological conditions is due on the one hand to the influence of thyroid hormones on carbohydrate, lipid metabolism and on the other hand the zobogenic effect of insulin on thyroid tissue. However, despite many scientific papers and population studies, the relationship between thyroid disease and components of the metabolic syndrome is still a matter of research, but in clinical practice, the results of these studies help to diagnose thyroid disease.

Acute effects of euglycemic-hyperinsulinemia on myocardial contractility in male mice.

Type 2 diabetes and obesity are associated with increased risk of cardiovascular disease, including heart failure. A hallmark of these dysmetabolic states is hyperinsulinemia and decreased cardiac reserve. However, the direct effects of hyperinsulinemia on myocardial function are incompletely understood. In this study, using invasive hemodynamics in mice, we studied the effects of short‐term euglycemic hyperinsulinemia on basal myocardial function and subsequent responses of the myocardium to β‐adrenergic stimulation. We found that cardiac function as measured by left ventricular (LV) invasive hemodynamics is not influenced by acute exposure to hyperinsulinemia, induced by an intravenous insulin injection with concurrent inotropic stimulation induced by β‐adrenergic stimulation secondary to isoproterenol administration. When animals were exposed to 120‐min of hyperinsulinemia by euglycemic‐hyperinsulinemic clamps, there was a significant decrease in LV developed pressure, perhaps secondary to the systemic vasodilatory effects of insulin. Despite the baseline reduction, the contractile response to β‐adrenergic stimulation remained intact in animals subject to euglycemic hyperinsulinemic clamps. β‐adrenergic activation of phospholamban phosphorylation was not impaired by hyperinsulinemia. These results suggest that short‐term hyperinsulinemia does not impair cardiac inotropic response to β‐adrenergic stimulation in vivo.

Differential regulation of insulin signalling by monomeric and oligomeric amyloid beta-peptide.

Alzheimer’s disease and Type 2 diabetes are pathological processes associated to ageing. Moreover, there are evidences supporting a mechanistic link between Alzheimer’s disease and insulin resistance (one of the first hallmarks of Type 2 diabetes). Regarding Alzheimer’s disease, amyloid β-peptide aggregation into β-sheets is the main hallmark of Alzheimer’s disease. At monomeric state, amyloid β-peptide is not toxic but its function in brain, if any, is unknown. Here we show, by in silico study, that monomeric amyloid β-peptide 1-40 shares the tertiary structure with insulin and is thereby able to bind and activate insulin receptor. We validated this prediction experimentally by treating human neuroblastoma cells with increasing concentrations of monomeric amyloid β-peptide 1-40. Our results confirm that monomeric amyloid β-peptide 1-40 activates insulin receptor autophosphorylation, triggering downstream enzyme phosphorylations and the glucose Transporter 4 translocation to the membrane. On the other hand, neuronal insulin resistance is known to be associated to Alzheimer’s disease since early stages. We thus modelled the docking of oligomeric amyloid β-peptide 1-40 to insulin receptor. We found that oligomeric amyloid β-peptide 1-40 blocks insulin receptor, impairing its activation. It was confirmed in vitro by observing the lack of insulin receptor autophosphorylation, and also the impairment of insulin-induced intracellular enzyme activations and the glucose Transporter 4 translocation to the membrane. By biological system analysis, we have carried out a mathematical model recapitulating the process that turns amyloid β-peptide binding to insulin receptor from the physiological to the pathophysiological regime. Our results suggest that monomeric amyloid β-peptide 1-40 contributes to mimic insulin effects in the brain, which could be good when neurons have an extra requirement of energy beside the well-known protective effects on insulin intracellular signalling, while its accumulation and subsequent oligomerization blocks the insulin receptor producing insulin resistance and compromising neuronal metabolism and protective pathways.

Effect of Topical Insulin Versus Normal Saline Dressing in Healing of Diabetic Foot Ulcers

Diabetic foot ulcer is a common cause of admission in the surgical wards and sometimes the first presentation of this debilitating disease. Numerous topical medication and gels are promoted for ulcer care and healing. Relatively few have proved to be more efficacious than normal saline dressing. This study aimed to compare the effect of topical insulin versus normal saline dressing in healing of diabetic foot ulcers at Rajshahi Medical College Hospital, Rajshahi.
 Aims and objectives: To assess the effect of topical insulin versus normal saline dressing in healing of diabetic foot ulcers.
 Methods: A total of 60 patients with diabetic foot ulcers were studied in different units of surgical ward of Rajshahi Medical College Hospital from July 2017 to June 2019. Patients were divided into two groups of 30 patients each that is group A (topical insulin) and group B (Normal saline). Ratio, mean, standard deviation, Pearson Chi-Square test were applied appropriately to this study.
 Results: Among the 60 patients, majority of the patients were males in both the groups (73.33% in group A and 80.00% in group B) with male to female ratio of 2.7:1 in group A and 4:1 in group B. The mean age in group A was 50.00±7.33 years and in group B it was 53.00±7.80 years, where P=1.00. Among patients with group A significant reduction of mean ulcer area was observed (314.30±171.26 mm2 ) with higher mean percentage reduction (15.30±3.28 percent), whereas, in group B the mean percentage reduction was significantly less (6.35±2.03 percent) with less reduction of mean final ulcer area (110.5±56.23mm2), where P<0.001.
 Conclusions: Topical insulin dressing provided better outcome in patients with diabetic foot ulcers by significant reduction in wound area when compared to normal saline dressing.
 Central Medical College Journal Vol 5 No 2 Jul 2021 PP 94-101

Insulin and Melatonin Modulates the Histo Architecture, Cellular Biochemistry and Receptor Expression During Injury of Hepatic in Diabetic individuals and its treatment

Objective: The purpose of this research was to examine the effects of exogenous melatonin and insulin on the biochemical, serological, histological, and receptor expression architecture of liver tissues in response to hepatic damage. Study Design: Observational study Place and Duration: This study was carried out at Hayatabad Medical Complex from November 2021 to March 2022 Methods: Total 72 patients of diabetes mellitus had age 19-78 years were presented in this study. All the patients had hepatic injury and admitted to outpatient department. After obtaining informed written consent detailed demographics of enrolled cases were recorded. Patients received melatonin and insulin therapy and continuous follow up was taken. Outcomes among all patients were recorded in terms of effectiveness. SPSS 23.0 was used to analyze all data. Results: Mean age of the patients was 42.13±16.42 years and had mean BMI 28.11±8.38 kg/m2.Most of the patients were from rural areas and were not educated. 45 (62.5%) were married and remaining 27 (37.5%) were not married. Majority patients 50 (69.4%) had diabetes mellitus-2. Other diseases were hypertension, pulmonary disease, respiratory and cardiac disease. As per liver function test, significant increased values were obtained in ALT, AST, ALP, serum cholesterol, LDL, VLD but decrease in HDL level. We found recovery of hepatic injury in 64 (88.9%) cases. Biochemical, cellular structure of liver cells, and the expression pattern of MT1, MT2, and IR receptors were all shown to have significantly recovered and restored. Conclusion: We concluded in this study that combine therapy of melatonin and insulin among diabetic patients of hepatic injury resulted significantly good results in terms of efficacy and disease recovery. Keywords: Diabetes Mellitus, Insulin, Melatonin, Efficacy, Hepatic Injury

METFORMIN OR INSULIN IN GESTATIONAL DIABETES-A CONUNDRUM

Objective: To determine the effectiveness of metformin vs insulin for glycemic control in gestational diabetes mellitus. Methodology: This study was done in the Department of Gynecology and Obstetrics, Saidu Teaching Hospital Swat from November 2019 to May 2020. Ethical approval was taken from the hospital ethical and research com­mittee. A sample of 93 patients in each group was taken as per WHO sample size calculation software. All female patients with singleton pregnancies having gestational diabetes diagnosed for the first time in current pregnancy with an age limit from 16-40 Years were included in this study. The lottery method was used for dividing patients into two groups, group A (Metformin) and group B (Insulin). SPSS 23.0 was used for the data analysis using fre­quencies and percentages and the Chi-Square test was used to compare the efficacy of drugs between the two study groups. Efficacy was checked by measuring 1-hour postprandial sugar levels, i-e; more or less than 140mg/ dl. A p-value less than or equal to 0.05 was considered statistically significant. Results: Total number of patients was 186 (93 in each group). The mean age in group A was 28±3.76 years compared to 27±3.13 years in group B. Good glycemic control out of our total 186 patients (93 in each group) was achieved in 80%(n-74) in Group A compared to 90% (n-84) in Group B with a p-value was 0.0403. Conclusion: The study concludes that metformin is non-inferior to insulin in controlling glucose levels in gesta­tional diabetes mellitus.

Myonectin in grass carp (Ctenopharyngodon idella): Molecular cloning and effect of nutrition state, insulin and glucagon on myonectin expression

As an endocrine organ, skeletal muscle secretes multiple myokines. Myonectin, a myokine, participates in lipid and glucose metabolism. To explore the functions of myonectin in teleosts, the myonectin gene was cloned from the brain tissue of grass carp. The open reading frame (ORF) of isolated myonectin was 813 bp, encoding 270 amino acids. Grass carp myonectin has four predicted domains: signal peptide, N-terminal domain (NTD), collagen protein domain, and C1q/TNF-like domain. In addition, four predicted glycosylation sites and four conserved cysteine residues were located in grass carp myonectin. Myonectin mRNA was detected in multiple tissues of grass carp and was highly expressed in the brain region, heart and kidney. In the oral glucose tolerance test (OGTT), myonectin mRNA levels were significantly induced in the kidney, hypothalamus, muscle and brain after treatment with glucose. In the fast and refeeding experiment, the serum glucose level was decreased in the fast group. However, serum glucose levels were increased in the refeeding group. The myonectin mRNA levels in the kidney, heart, brain and liver were significantly reduced in the fast groups. Moreover, the myonectin expression was markedly increased in the refeeding groups. In grass carp primary hepatocytes, myonectin mRNA levels were induced by treatment with glucose and oleic acid for 12 or 24 h. Myonectin expression was dramatically promoted by treatment with insulin. Moreover, myonectin expression was markedly decreased with glucagon treatment in primary hepatocytes. The results of this study will provide a basis for exploring the roles of grass carp myonectin in the future.

A Dioscorea opposita Thunb Polysaccharide-Based Dual-Responsive Hydrogel for Insulin Controlled Release

A novel hydrogel (DOP/PEI-PBA) based on the “three-component” reaction of 2-formylphenylboric acid (2-FPBA), the primary amine group of polyethyleneimine (PEI) and the cis-o-dihydroxy groups of Dioscorea opposita Thunb polysaccharide (DOP) was designed in this work. The hydrogel can be easily prepared by simply mixing the three reactants at room temperature. The hydrogel had dual responsiveness to glucose and pH, and can realize the controllable release of insulin. Moreover, the hydrogel combining insulin and DOP can inhibit the reactive oxygen species (ROS) level and malondialdehyde (MDA) content, and promote glucose consumption as well as the level of superoxide dismutase (SOD), in high-glucose-induced injury in HL-7702 cells, which reflects the synergistic effect of insulin and DOP to protect hepatocytes from oxidative stress at the same time. Further in vitro cytotoxicity studies showed that the hydrogel had good biocompatibility and no obvious toxicity to cells. These indicate that the prepared hydrogel (DOP/PEI-PBA) can be expected to be applied in the clinical treatment of insulin deficiency in diabetes.

Insulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity

ObjectiveMaternal obesity increases the incidence of excess adiposity in newborns, resulting in lifelong diabetes risk. Elevated intrauterine fetal adiposity has been attributed to maternal hyperglycemia; however, this hypothesis does not account for the increased adiposity seen in newborns of mothers with obesity who have euglycemia. We aimed to explore the placental response to maternal hyperinsulinemia and the effect of insulin-like growth factor 2 (IGF-2) in promoting fetal adiposity by increasing storage and availability of nutrients to the fetus. MethodsWe used placental villous explants and isolated trophoblasts from normal weight and obese women to assess the effect of insulin and IGF-2 on triglyceride content and insulin receptor signaling. Stable isotope tracer methods were used ex vivo to determine effect of hormone treatment on de novo lipogenesis (DNL), fatty acid uptake, fatty acid oxidation, and esterification in the placenta. ResultsHere we show that placentae from euglycemic women with normal weight and obesity both have abundant insulin receptor. Placental depth and triglyceride were greater in women with obesity compared with normal weight women. In syncytialized placental trophoblasts and villous explants, insulin and IGF-2 activate insulin receptor, induce expression of lipogenic transcription factor SREBP-1 (sterol regulatory element-binding protein 1), and stimulate triglyceride accumulation. We demonstrate elevated triglyceride is attributable to increased esterification of fatty acids, without contribution from DNL and without an acceleration of fatty acid uptake. ConclusionsOur work reveals that obesity-driven aberrations in maternal metabolism, such as hyperinsulinemia, alter placental metabolism in euglycemic conditions, and may explain the higher prevalence of excess adiposity in the newborns of obese women.

Studi Kasus : Fenomena Fajar dan Efek Somogyi pada Pasien Diabetes di Lihat dari Kadar Gula Darah dan Masalah Keperawatan yang Muncul di Filipina

Early morning hyperglycaemia in diabetics can be caused by the dawn phenomenon, the Somogyi effect, or poor glycaemic control. The dawn phenomenon occurs when endogenous insulin secretion decreases or when the effect of exogenous insulin given to the patient the day before disappears, along with a physiological increase in insulin antagonist hormone. When people with diabetes eat too late at night, consume alcohol, or use insulin too late, it will cause a spike in blood sugar levels in the morning. This condition is known as the Somogyi effect and is caused by the human activity itself. The Somogyi effect is present in the case of excessive amounts of exogenous insulin. The dawn phenomenon is more common than the Somogyi effect. This research method uses a case study to explore the problem of nursing care in patients with diabetes mellitus at St Paul University Hospital, Philippines. Data were collected using interviews, observation, physical examination, and documentation. The data obtained were analysed by descriptive method, compiled from diagnosis to evaluation using three diabetic patients as sampling. To diagnose this dawn phenomenon, it is important for nurses to measure plasma glucose levels over several nights between 3 am and 5 am or use a continuous glucose monitoring system. Although the treatments are different, the best way to prevent the dawn phenomenon and the Somogyi effect is to control diabetes optimally with insulin therapy. It is hoped that nurses, clients, and families can monitor the patient's glucose levels periodically to prevent complications in diabetes.
 Keywords : Diabetic, Somogyi, Down Phenomenon Effect, case study

Insulin prevents fatty acid induced increase of adipocyte size

ABSTRACT Metabolic disorders related to obesity are largely dependent on adipose tissue hypertrophy, which involves adipocyte hypertrophy and increased adipogenesis. Adiposize is regulated by lipid accumulation as a result of increased lipogenesis (mainly lipid uptake in mature adipocytes) and reduced lipolysis. Using realtime 2D cell culture analyses of lipid uptake, we show 1) that high glucose concentration (4.5 g/L) was required to accumulate oleic acid increasing lipid droplet size until unilocularisation similar to mature adipocytes in few days, 2) oleic acid reduced Peroxisome-Proliferator Activated Receptor Gamma (PPARG) gene transcription and 3) insulin counteracted oleic acid-induced increase of lipid droplet size. Although the lipolytic activity observed in high versus low glucose (1g/L) conditions was not altered, insulin was found to inhibit oleic acid induced gene transcription required for lipid storage such as CIDEC (Cell Death Inducing DFFA Like Effectors) and G0S2 (G0 switch gene S2), possibly through PPARA activity. Although this signaling pathway requires more detailed investigation, the results point out the differential mechanisms involved in the pro-adipogenic effect of insulin in absence versus its protective effect on adiposity in presence of oleic acid uptake.

Pioglitazone in diabetic kidney disease: forgotten but not gone.

Diabetic kidney disease (DKD) is described in approximately 20–40% of all diabetic patients and is associated with significant cardiovascular and all-cause mortality. The involvement of multiple metabolic, haemodynamic, inflammatory, and tubular pathways in the pathophysiology of DKD generates the need for multitargeted treatment approaches to improve its development at all levels and delay or even reverse its progression. Thiazolidinediones are potent exogenous agonists of PPAR-γ, which augment the effects of insulin on its cellular targets, mainly at the level of adipose tissue. Pioglitazone, currently the main thiazolidinedione in clinical practice, has achieved significant improvements of albuminuria in patients with type 2 diabetes. It can also interfere with most cellular pathways involved in the development and evolution of DKD. This paper explores the pathophysiological mechanisms governing its possible nephroprotective activity during a diabetic state. It also discusses its future role to ameliorate the global burden of DKD.

Effect of vitamin E on oxidative stress indicated by serum malondialdehyde and Paroxonase level in type 2 diabetes mellitus with retinopathy

Background: Type 2 diabetes mellitus is a progressive condition in which the body becomes resistant to the normal effects of insulin and/or gradually loses the capacity to produce enough insulin the pancreas. Objectives: This case-control study was conducted to assess the effect of vitamin E on oxidative stress indicated by malondialdehyde and paronxanase 1 level on T2DM patients with retinopathy. Patients and Methods: Two equal groups each consisted of thirty patients; the 1st group was T2DM without retinopathy (control) and the 2nd one was T2DM with retinopathy (case). Results: There was statistically significant positive correlation Oppositely, paroxanase 1 level was statistically significantly negatively correlated with hydroperoxidase. As. Also, there was statistically significant increase on paroxanase 1 level after 3-month vitamin E application as an antioxidant among the T2DM with retinopathy group. Conclusion: Serum MDA levels were associated with DR stage, suggesting that oxidative stress play a significant role in DR progression. On the other hand, MDA levels were reduced and proliferative DR patients after vitamin E intake for 3 months.

The effect of insulin, leptin, adiponectin, ghrelin levels in cord blood on growth in the first two years

Objective: The main hormones and adipokines that regulate growth, energy metabolism and adipogenesis in the intrauterine period are insulin, leptin, ghrelin, and adiponectin. Changes in these hormones and adipokines may affect weight gain, obesity and metabolic syndrome in advanced ages. In this study, it was aimed to investigate the relationship between insulin, leptin, ghrelin, adiponectin levels in the cord blood of term newborns and growth in the first two years of age. Methods: Term newborns in our hospital between May 2019 and October 2019 were included in the study. Insulin, glucose, ghrelin, leptin and adiponectin levels were studied in the umbilical cord blood of 80 newborns. The growth of 44 of the 80 newborns included in the study was monitored until the age of two years. Results: The relationship between insulin, ghrelin, leptin and adiponectin levels in the cord blood of 44 newborns included in the study with growth up to two years of age was investigated. A positive correlation was found between the insulin level in the cord blood and birth weight, birth head circumference, and the weights at the 12th and 24th months of life. A negative correlation was found between the level of ghrelin in the cord blood and the weights at the 6th and 24th months of life. A positive correlation was found between the level of adiponectin in the cord blood and the weight in the 6th month of life. There was no significant correlation between cord leptin level and anthropometric measurements in the first two years of age. Conclusion: While the levels of insulin and adiponectin in the cord blood were positively correlated with the weight in the first two years of life, they were negatively correlated with the ghrelin level in the cord blood. The level of leptin in cord blood did not correlate significantly with the weight in the first two years of life.

The p66Shc Protein Mediates Insulin Resistance and Secretory Dysfunction in Pancreatic β-Cells Under Lipotoxic Conditions.

We evaluated the role of the p66Shc redox adaptor protein in pancreatic β-cell insulin resistance that develops under lipotoxic conditions and with excess body fat. Prolonged exposure to palmitate in vitro or the presence of overweight/obesity augmented p66Shc expression levels and caused an impaired ability of exogenous insulin to increase cellular insulin content and secreted C-peptide levels in INS-1E cells and human and murine islets. In INS-1E cells, p66Shc knockdown resulted in enhanced insulin-induced augmentation of insulin content and C-peptide secretion and prevented the ability of palmitate to impair these effects of insulin. Conversely, p66Shc overexpression impaired insulin-induced augmentation of insulin content and C-peptide secretion in both the absence and presence of palmitate. Under lipotoxic condition, the effects of p66Shc are mediated by a p53-induced increase in p66Shc protein levels and JNK-induced p66Shc phosphorylation at Ser36 and appear to involve the phosphorylation of the ribosomal protein S6 kinase at Thr389 and of insulin receptor substrate 1 at Ser307, resulting in the inhibition of insulin-stimulated protein kinase B phosphorylation at Ser473. Thus, the p66Shc protein mediates the impaired β-cell function and insulin resistance induced by saturated fatty acids and excess body fat.

Using Convolutional Neural Network as a Statistical Algorithm to Explore the Therapeutic Effect of Insulin Liposomes on Corneal Inflammation.

Aiming at the disadvantages of easy recurrence of keratitis, difficult eradication by surgery, and easy bacterial resistance, insulin-loaded liposomes were prepared, and convolutional neural network was used as a statistical algorithm to build SD rat corneal inflammation model and study insulin-loaded liposomes, alleviating effect on corneal inflammatory structure in SD rats. The INS/PFOB@LIP was developed by means of thin-film dispersive phacoemulsification, its structure was monitored using a transmission electron microscope, particle size and appearance potential were monitored using a Malvern particle sizer, and ultraviolet consumption spectrum was monitored using a UV spectrophotometer. The encapsulation rate, drug loading, and distribution of insulin liposomes in rat corneal inflammatory model were measured and calculated. The cytotoxicity of liposome materials was evaluated by CCK-8 assay, and the toxic effects of insulin and insulin liposomes on cells were detected. The cornea of SD rats was burned with NaOH solution (1 mol/L), and the SD rat corneal inflammation model was created. The insulin liposome was applied to the corneal inflammation model, and the therapeutic effect of insulin liposome on corneal inflammation was evaluated by slit lamp, corneal immunohistochemistry, corneal HE staining, and corneal Sirius red staining. Insulin-loaded liposomes were successfully constructed with an average particle size of (130.69 ± 3.87) nm and a surface potential of (−38.24 ± 2.57) mV. The encapsulation rate of insulin liposomes was (48.89 ± 1.24)%, and the drug loading rate was (24.45 ± 1.24)%. The SD rat corneal inflammation model was successfully established. After insulin liposome treatment, the staining area of corneal fluorescein sodium was significantly reduced, the corneal epithelium was significantly thickened, the content of corneal collagen was increased, the expression of inflammatory factors was significantly reduced, and new blood vessels (corneal neovascularization, CNV) growth was inhibited.

Intensification of Insulin Treatment With Insulin Degludec/Aspart in Type 2 Diabetic Patients: A 2-Year Real-World Experience.

To evaluate the effects of insulin degludec/insulin aspart (IDegAsp) coformulation as an intensification of insulin treatment for glycemic control in patients with type 2 diabetes (T2D) in a long term real-world clinical setting. This retrospective non-interventional study, included 210 patients with T2D who to IDegAsp coformulation from prior insulin treatment in a tertiary endocrinology center between September 2017 and December 2019. The baseline data was taken as the index date and defined as the first IDegAsp prescription claim. Previous insulin treatment modalities, hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight were recorded, respectively at the 3rd, 6th, 12th, and 24th months of the IDegAsp treatment. Out of the total 210 patients, 166 patients under insulin treatment switched to twice-daily IDegAsp treatment, 35 patients switched to once daily IDegAsp and twice premeal short-acting insulin regimen as a modified basal-bolus (BB) treatment, and nine patients commenced with once-daily IDegAsp treatment. HbA1c decreased from 9.2% ± 1.9% to 8.2% ± 1.6% in 6 months, 8.2% ± 1.7% in the first year, and 8.1% ± 1.6% in the second year of the therapy (p< 0.001). FPG decreased from 209.0 ± 85.0 mg/dL to 147.0 ± 62.6 mg/dL in the second year (p< 0.001). The required total daily dose of insulin increased in the second year of IDegAsp treatment compared to baseline. However, there was a borderline significance increase in IDegAsp requirement for the whole group at the two-year follow-up (p = 0.05). Patients who were administered twice daily IDegAsp injections required more total insulin in the first and second years due to added premeal short-acting insulin injections (p < 0.05). The frequency of patients with HbA1c < 7% was 31.8% in first year and 35.8% in second year under IDegAsp treatment.Insulin dose was de-escalated in 28.5% of the patients under BB treatment, while 15% under twice-daily IDegAsp required increased BB treatment. Intensification of insulin treatment with IDegAsp coformulation improved glycemic control in patients with T2D. The total daily insulin requirement increased but the IDegAsp requirement lightly increased at the two-year follow-up. Patients under BB treatment required de-escalation of insulin treatment.

Insulin infusion decreases medium-sized extracellular vesicles in adults with metabolic syndrome.

Elevated extracellular vesicles (EVs) are associated with glucose dysmetabolism. However, the effects of insulin on EVs and subsequent relationships with insulin sensitivity, substrate oxidation, and inflammation are unknown. We tested the hypothesis that insulin would lower EVs and relate to insulin action. Fifty-one sedentary adults (54.8 ± 1.0 yr; V̇o2peak : 22.1 ± 0.6 mL/kg/min) with metabolic syndrome (MetS) and obesity (36.4 ± 0.65 kg/m2) underwent a 2-h euglycemic-hyperinsulinemic clamp (5 mmol/L; 40 mU/m2/min). Count and size (medium: 200-624 nm; larger: 625-1,000 nm) for total particle count, endothelial- (CD105+), leukocyte- (CD45+), platelet- (CD41+), and tetraspanin- (TX+: CD9/CD81/CD63), as well as platelet endothelial cell adhesion molecule- (CD31+) derived EVs were determined before and following the clamp using Full Spectrum Profiling (FSPM). Size and MESF (molecules of equivalent soluble fluorochrome) data were generated using FCMPASS Software. Fat and carbohydrate oxidation, in addition to high-sensitivity c-reactive protein (hsCRP), were measured to understand insulin effects and associations between EVs, metabolic flexibility, and inflammation. Despite low metabolic insulin sensitivity (M-Value = 2.56 ± 0.17 mg/kg/min), insulin increased carbohydrate (P = 0.015) and decreased fat oxidation (P = 0.048) and hsCRP (P = 0.016) compared with fasting. Insulin also decreased total particle count (P < 0.001), attributable to decreased medium-sized CD105+ (P = 0.052) and CD45+ EVs (P < 0.001). Elevated fasting insulin was associated with reduced insulin-stimulated changes in all EVs phenotypes (P < 0.001). Interestingly, fasting EVs were associated with increased fasting carbohydrate oxidation (all P < 0.05). These findings suggest that insulin decreases medium-sized EVs in conjunction with metabolic flexibility under euglycemic conditions in adults with MetS. More research is needed to determine how therapies alter EV phenotype/size and consequent cardiometabolic risk.NEW & NOTEWORTHY This study is one of the first to investigate the effects of insulin on medium and larger extracellular vesicles (EVs) in relation to metabolic insulin sensitivity and fuel use in adults with metabolic syndrome. Our data suggest that insulin infusion decreases the concentration of total particle counts, mainly due to reductions in medium-sized EVs. Furthermore, EVs, predominantly medium-sized, are inversely associated with metabolic flexibility.

The insulin receptor family in the heart: new light on old insights.

Insulin was discovered over 100 years ago. Whilst the first half century defined many of the physiological effects of insulin, the second emphasised the mechanisms by which it elicits these effects, implicating a vast array of G proteins and their regulators, lipid and protein kinases and counteracting phosphatases, and more. Potential growth-promoting and protective effects of insulin on the heart emerged from studies of carbohydrate metabolism in the 1960s, but the insulin receptors (and the related receptor for insulin-like growth factors 1 and 2) were not defined until the 1980s. A related third receptor, the insulin receptor-related receptor remained an orphan receptor for many years until it was identified as an alkali-sensor. The mechanisms by which these receptors and the plethora of downstream signalling molecules confer cardioprotection remain elusive. Here, we review important aspects of the effects of the three insulin receptor family members in the heart. Metabolic studies are set in the context of what is now known of insulin receptor family signalling and the role of protein kinase B (PKB or Akt), and the relationship between this and cardiomyocyte survival versus death is discussed. PKB/Akt phosphorylates numerous substrates with potential for cardioprotection in the contractile cardiomyocytes and cardiac non-myocytes. Our overall conclusion is that the effects of insulin on glucose metabolism that were initially identified remain highly pertinent in managing cardiomyocyte energetics and preservation of function. This alone provides a high level of cardioprotection in the face of pathophysiological stressors such as ischaemia and myocardial infarction.