Higher Insulin Levels Research Articles

Decreased Insulin and Interleukin-6 Levels in Rattus Norvegicus Model of Polycystic Ovary Syndrome-Insulin Resistance Treated with a High Protein Diet

Hypercaloric in women of childbearing age is one of the causes of polycystic ovary syndrome (PCOS) with insulin resistance. Increased inflammation (tumor factor necrosis-α (TNF-α) and interleukin-6 (IL-6)) is the impact of endocrine and metabolic disorders involved due to metabolic syndrome, obesity, and diabetes mellitus. This study aims to evaluate whether a high-protein diet can reduce insulin and interleukin-6 levels, which are key indicators of polycystic ovary syndrome, and whether these changes can help in the treatment of the syndrome. This study used a prepost test only control design, true experimental, with a total sample of 6 female Rattus norvegicus rats aged 2–3 years (150–200 g). It consists of 4 groups, namely the negative control group (K-), the positive control group (K+), the treatment group (P), and the group without treatment (P-). The study examined the rat blood serum ELISA measurement of insulin and IL-6 levels. Anova test results of IL-6 levels (p = 0.002). Post-hoc test results of group K- and group P (p = 0.002), group K + and group P (p = 0.037), group K- and group K + (p = 0.437). The Anova test results of insulin levels between groups found a significant difference (p = 0.001). Post-hoc test of insulin levels of group K- and group P (p = 0.002), group K- and group K+ (p = 0.000), and group K+ with group P (p = 0.356). In group K and group P, the results of the ANOVA and post hoc tests on IL-6 levels and insulin levels with the provision of a high-protein diet show significant differences. This study suggests that a high-protein diet may be an effective therapeutic alternative in reducing the symptoms of polycystic ovary syndrome, especially in controlling high insulin and interleukin-6 levels.

9260 Insulin Receptor Signaling And Racial Disparities In Triple Negative Breast Cancer

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P<0.05 for all). Positive IGF1R, FOXO3a, pERK staining were not associated with any of these factors. Conclusions: We found that 64% of TNBCs had positive expression of IR, and IR expression was more prevalent in tumors from Black women and associated with higher insulin levels, suggesting that tumors from Black women may be more sensitive to the tumor promoting effects of systemic hyperinsulinemia. Presentation: 6/2/2024

8212 Insulin Receptor Signaling and Racial Disparities in Triple Negative Breast Cancer

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P<0.05 for all). Positive IGF1R, FOXO3a, pERK staining were not associated with any of these factors. Conclusions: We found that 64% of TNBCs had positive expression of IR, and IR expression was more prevalent in tumors from Black women and associated with higher insulin levels, suggesting that tumors from Black women may be more sensitive to the tumor promoting effects of systemic hyperinsulinemia. Presentation: 6/2/2024

9260 Insulin Receptor Signaling and Racial Disparities in Triple Negative Breast Cancer

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P<0.05 for all). Positive IGF1R, FOXO3a, pERK staining were not associated with any of these factors. Conclusions: We found that 64% of TNBCs had positive expression of IR, and IR expression was more prevalent in tumors from Black women and associated with higher insulin levels, suggesting that tumors from Black women may be more sensitive to the tumor promoting effects of systemic hyperinsulinemia. Presentation: 6/2/2024

8212 Insulin Receptor Signaling And Racial Disparities In Triple Negative Breast Cancer

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P<0.05 for all). Positive IGF1R, FOXO3a, pERK staining were not associated with any of these factors. Conclusions: We found that 64% of TNBCs had positive expression of IR, and IR expression was more prevalent in tumors from Black women and associated with higher insulin levels, suggesting that tumors from Black women may be more sensitive to the tumor promoting effects of systemic hyperinsulinemia. Presentation: 6/2/2024

7378 Glargine Induced Neuroglycopenia in Patients with End-Stage Renal Disease: Importance of Insulin Regimen Optimization in Haemodialysis Patients

Abstract Disclosure: M. Shrivastava: None. L. Kaur: None. B. Armendariz: None. R. Kaur: None. A. Shetty: None. In patients with end stage renal disease (ESRD), hypoglycemia accounts for up to 3.6% of all the admissions with mortality rates of up to 30%. A combination of impaired insulin clearance, changes in glucose metabolism and dialysis process makes the patients with end stage renal disease vulnerable to neuroglycopenia.Case description:53 year old female with past medical history of insulin dependent type 2 diabetes mellitus, ESRD secondary to diabetes, on hemodialysis(HD) thrice weekly since two years, presented to the emergency with altered mental status, respiratory distress, tachycardia. Lab work revealed blood glucose(BG) of 23 mg/dl, HbA1c of 8.4%, eGFR of 6, and arterial blood gas showed hypercapnic respiratory acidosis. Patient received dextrose, with no improvement of symptoms. Eventually she developed acute hypercapnic respiratory failure requiring endotracheal intubation with mechanical ventilation, and was transferred to the ICU. As per family, a night prior to presentation, last recorded BG after dinner was 253 mg/dl, she took her night time glargine, which was recently increased by her primary care for poorly controlled HbA1c levels. Brain MRI and long term EEG monitoring findings were consistent with underlying extensive brain injury secondary to prolonged hypoglycemia. Unfortunately, the patient's condition did not improve despite HD and BG correction, eventually she underwent compassionate extubation. Case Discussion:The insulin requirements in ESRD patients are reduced by approximately 50%, regardless of residual insulin secretion. Malnutrition and acidosis reduce hepatic glycogen stores and availability of gluconeogenic precursor, expected compensatory renal gluconeogenesis is compromised by decreased renal function causing hypoglycemia, which is further worsened by inappropriately high plasma insulin levels caused by reduced renal insulin breakdown. Diabetes mellitus patients with ESRD are frequently managed with basal-bolus insulin regimen, and HD up to thrice weekly, leaving them without HD for up to 3 days especially over the weekend. This can result in accumulation of insulin metabolites causing delayed insulin clearance as seen in our patient. In such cases even long acting insulin, such as glargine, can have compounding effects, which could possibly cause fatal complications such as neuroglycopenia. In such patients continuous glucose monitor use with tapering dose glargine regimen may help eliminate this compounding effect. Conclusion: Neuroglycopenia is a rare manifestation of diabetes mellitus with ESRD. Compromised renal gluconeogenesis and impaired insulin clearance can cause inappropriately high plasma levels of insulin. In such patients continuous glucose monitoring along with tapering dose of long acting insulin should be utilized for proper glycemic control to limit compounded effect of insulin metabolite accumulation. Presentation: 6/3/2024

Mammalian D-Cysteine controls insulin secretion in the pancreas

D-amino acids are being recognized as important molecules in mammals with function. This is a first identification of endogenous D-cysteine in mammalian pancreas. D-cysteine is synthesized by serine racemase (SR) and SR−/− mice produce 6–10 fold higher levels of insulin in the pancreas and plasma including higher glycogen and ketone bodies in the liver. The excess insulin is stored as amyloid in secretory vesicles and exosomes. In glucose stimulated insulin secretion in mouse and human islets, equimolar amount of D-cysteine showed higher inhibition of insulin secretion compared to D-serine, another closely related stereoisomer synthesized by SR. In mouse models of diabetes (Streptozotocin (STZ) and Non Obese Diabetes (NOD) and human pancreas, the diabetic state showed increased expression of D-cysteine compared to D-serine followed by increased expression of SR. SR−/− mice show decreased cAMP in the pancreas, lower DNA methyltransferase enzymatic and promoter activities followed by reduced phosphorylation of CREB (S133), resulting in decreased methylation of the Ins1 promoter. D-cysteine is efficiently metabolized by D-amino acid oxidase and transported by ASCT2 and Asc1. Dietary supplementation with methyl donors restored the high insulin levels and low DNMT enzymatic activity in SR−/− mice. Our data show that endogenous D-cysteine in the mammalian pancreas is a regulator of insulin secretion.

Simultaneous determination and association between serum levels of irisin and chemerin in PCOS.

To determine the serum levels of irisin, chemerin and insulin in women with polycystic ovary syndrome, and to compare their levels with respect to bodyweight and body mass index. The case-control study was conducted at the Department of Clinical Chemistry, College of Medicine, Mustansiriyah University, Baghdad, Iraq, from December 2020 to February 2022, and comprised healthy controls in group I who were matched for bodyweight and body mass index with polycystic ovary syndrome women in group II. Subjects and cases were inducted using purposive sampling technique Subgroups were also formed on the basis of normal body mass index, and overweight-obese status. Serum irisin, chemerin, insulin and free testosterone levels, anthropometric measurements, lipid profile as well as hormonal and biochemical parameters were noted. Data was analysed using SPSS 25. Of the 88 subjects, 32(36.4%) were in group I with mean age 25.1±4.7 years, and 56(63.6%) in group II with mean age 25.0±6.3 years (p>0.05). Both the groups were divided into two equal subgroups A and B. Group II had significantly higher mean body mass index (p=0.007) and adult body fat (p=0.018). Group II women had significantly high fasting serum insulin levels (p<0.001) and homeostatic model assessment for insulin resistance values (p<0.001). Serum irisin had significant positive correlation with serum chemerin (p=0.014) in group II. Serum free testosterone, irisin and chemerin were significantly higher (p<0.001) in group II compared to group I except for chemerin which showed no significant differences among women with normal body mass index (p=0.071). Serum levels of irisin and chemerin could serve as biomarkers of polycystic ovary syndrome.

Higher peak height velocity in early maturing girls depends on insulin rather than fat mass or IGF-I

Abstract Objective Age at pubertal onset has decreased over the recent decades. Early maturing girls have longer puberty duration, and higher peak height velocity (PHV) than late maturing girls. To what extent this is generated by increased insulin-like growth factor-I (IGF-I), fat mass, or fasting insulin levels is currently unknown. Design, setting, participants A population-based study—part of the COPENHAGEN puberty study—longitudinal part. Eighty-one girls evaluated biannually for a median of 10 (2-15) visits for a total of 815 evaluations. Methods Pubertal staging, anthropometric measures, PHV, skin fold thickness (SFT), and IGF-I and fasting insulin levels were measured. Results Early maturing girls achieved similar final height compared to late maturing girls (166.1 vs 167.1 cm, P = .36). Early pubertal onset was associated with significantly greater PHV (8.7 vs 7.4 cm/year, P &amp;lt; .001) and a longer puberty duration (age at onset of breast development to age at PHV [1.8 vs 1.1 years, P &amp;lt; .001]) compared with late maturation. After correcting for age at pubertal onset, neither body mass index, SFT, nor IGF-I levels differed between early vs late maturing girls. By contrast, fasting insulin levels were significantly higher in early compared with late maturing girls 1.5, 2.0, and 3.0 years after pubertal onset (all P = .039). Conclusion Growth velocity was higher and more prolonged in early compared with late maturing girls and associated with higher insulin levels. Thus, the higher insulin levels may compensate for the shorter total growth period by intensifying the pubertal growth period. Clinical trial registration number NCT01411527.

GTPBP8 mitigates nonalcoholic steatohepatitis (NASH) by depressing hepatic oxidative stress and mitochondrial dysfunction via PGC-1α signaling

Nonalcoholic steatohepatitis (NASH) is emerging as a major cause of liver transplantation and hepatocellular carcinoma (HCC). Regrettably, its pathological mechanisms are still not fully comprehended. GTP-binding protein 8 (GTPBP8), belonging to the GTP-binding protein superfamily, assumes a crucial role in RNA metabolism, cell proliferation, differentiation, and signal transduction. Its aberrant expression is associated with oxidative stress and mitochondrial dysfunctions. Nevertheless, its specific functions and mechanisms of action, particularly in NASH, remain elusive. In our current study, we initially discovered that human hepatocytes L02 displayed evident mitochondrial respiratory anomaly, mitochondrial damage, and dysfunction upon treatment with palmitic acids and oleic acids (PO), accompanied by significantly reduced GTPBP8 expression levels through RNA-Seq, RT-qPCR, western blotting, and immunofluorescence assays. We then demonstrated that GTPBP8 overexpression mediated by adenovirus vector (Ad-GTPBP8) markedly attenuate lipid accumulation, inflammatory response, and mitochondrial impair and dysfunction in hepatocytes stimulated by PO. Conversely, adenovirus vector-mediated GTPBP8 knockdown (Ad-shGTPBP8) significantly accelerated lipid deposition, inflammation and mitochondrial damage in PO-treated hepatocytes in vitro. Furthermore, we constructed an in vivo NASH murine model by giving a 16-week high fat high cholesterol diet (HFHC) diet to hepatocyte specific GTPBP8-knockout (GTPBP8HKO) mice. We firstly found that HFHC feeding led to metabolic disorder in mice, including high body weight, blood glucose and insulin levels, and liver dysfunctions, which were accelerated in these NASH mice with GTPBP8 deficiency in hepatocytes. Consistently, GTPBP8HKO remarkably exacerbated the progression of NASH phenotypes induced by HFHC, as proved by the anabatic lipid accumulation, inflammation, fibrosis and reactive oxygen species (ROS) production in liver tissues, which could be largely attributed to the severe mitochondrial damage and dysfunction. Mechanistically, we further identified that GTPBP8 interacted with peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in hepatocytes. Importantly, the hepaprotective effects of GTPBP8 against mitochondrial dysfunction, oxidative stress and inflammation was largely dependent on PGC-1α expression. Collectively, GTPBP8 may exert a protective role in the progression of NASH, and targeting the GTPBP8/PGC-1α axis may represent a potential strategy for NASH treatment by improving mitochondrial functions.

Exploring Factors Influencing Stroke Risk: Insights From a Predictive Analysis.

Introduction Stroke is a serious medical condition characterized by the sudden interruption of blood flow to the brain, resulting in the death of brain cells. It is a leading cause of long-term disability and mortality worldwide. Stroke has some associated risk factors, both modifiable and non-modifiable ones.As for non-modifiable risk factors, these are age, gender (men are more vulnerable), and family history of stroke.The controllable or adjustable risk factors include hypertension (high blood pressure), diabetes, smoking, high cholesterol levels, obesity, and insulin resistance. Methods In our study, we collected data from 229 patients which were originally collected for clinical purposes and were retrospectively analyzed. These data contain features such assex and age, the presence of ischemic heart disease (IHD) or stroke history, and different blood sugar readings. These measurements include fasting blood sugar (FBS), postprandial blood sugar (PPBS), HbA1c%, and insulin levels (fasting and postprandial).Furthermore, cholesterol was also tested, such as total cholesterol, triglycerides (TGL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL). Surprisingly, stroke was observed in 24of the 205 patients. This contrast permits us to be concerned with the chance of the association between stroke and insulin levels. Given the imbalanced nature of our outcome variable (stroke occurrence), the primary analytical method will be logistic regression. Results In this cross-sectional study, we investigated the association between high insulin levels (both fasting and postprandial) and the occurrence of stroke within a dataset of 229 patients. Out of the 229 included cases, 102 individuals were female (44.5%) and 127 individuals were male (55.5%). Twenty-four cases have ischemic heart disease (10.5%). Among the analyzed cases, 24 individuals have a history of stroke. The average age of the sample is approximately 57 years ± 14.87. There was no significant difference between the males and females in most of the descriptive statistics. However, females experienced significantly higher levels of postprandial glucose level and significantly lower levels of postprandial insulin. According to our predictive model, we found that an increase in fasting insulin levels was linked to a lower risk of stroke occurrence. On the other hand, increasing insulin postprandial levels and age were associated with an increased risk of stroke. Conclusion Our study identified age, fasting insulin, and postprandial insulin as key factors influencing stroke risk. Higher fasting insulin levels were associated with reduced risk, while increased postprandial insulin and age were linked to higher risk. Blood glucose, cholesterol, and triglycerides had minor effects. Notably, higher total cholesterol and triglyceride levels were slightly associated with lower stroke occurrence. Further research with larger samples is needed for validation.

Targeting cancer stress-associated hyperinsulinemia and abnormal behavior mitigates lung carcinoma in postmenopausal mouse: Intervention function of peimine

Obesity stress and its associated metabolic disruption increase the likelihood and advancement of several forms of malignancies, such as postmenopausal lung cancer in humans. Also, the mechanism of lung cancer stress-related cognitive impairment and rhythm change are still unknown. Peimine (PE), an alkaloid derived from the Fritillaria genus, has the ability to mitigate the metabolic dysfunctions induced by obesity and inhibit tumor growth. The objective of this study was to investigate the regulatory impact of PE on obese mice with postmenopausal lung cancer generated by a high fat diet. Our initial findings indicate that PE can significantly reduce the metabolic dysfunction caused by a high-fat diet in mice. This is demonstrated by better glucose tolerance and insulin resistance, reduced accumulation of lipids in the liver, and improved histological alterations in the mammary fat pad. Subsequently, the treatment of PE suppressed the formation of lung tumors caused by a high-fat diet in mice models placed in their original location. In addition, PE effectively inhibited the formation of pre-existing lung tumors in a mouse model of postmenopausal women who were fed a high-fat diet. This treatment also reduced the severity of metabolic problems. Notably, laboratory studies demonstrated that insulin exposure increased the growth and movement of lung cancer cells, but this effect was significantly reduced when the cells were co-cultured with PE. Meanwhile, PE intervention can significantly alleviate cancer stress-related cognitive impairment and disturbed circadian rhythm changes and associated gene expression abnormalities in model animals. Analysis using bioinformatics and molecular biology techniques revealed that PE has the ability to decrease the expression levels of signal transducer and activator of transcription 3 (STAT3) in the liver, mammary fat pad, and tumor tissues of postmenopausal mice with obesity generated by a high-fat diet. The inhibitory effects of PE on the growth and movement of lung cancer cells induced by insulin were completely eliminated when STAT3 expression was removed. This suggests that the suppression of STAT3 expression is crucial for PE to exert its anti-cancer effects against lung cancer in the presence of high insulin levels. The findings of our study indicate that consuming PE is highly effective in preventing and treating lung cancer that is connected with obesity. This is achieved via regulating the signaling pathway of STAT3.

دور داء السكري في متلازمة تكيس المبايض PCOS

The study focused on the insulin and its relationship with the Polycystic Ovary Syndrome (PCOS) in women. Where was it collected 44 samples of PCOS women and 46 samples as a control group. The results showed a significant decrease in progesterone at (P = 0.001), in women with PCOS. The findings in this study revealed the presence of a link between high insulin levels and polycystic ovarian syndrome, the statistical results demonstrate a positive significant association between insulin and estrogen at (p=0.001), and also found a significant negative correlation between other clinical parameter with insulin at, for those with the syndrome, due to the high level of insulin in their blood and the inability of female hormones and Insulin Antibody (AIA), to play their role in controlling the insulin and blood sugar level. Finally, the study showed that there is a new strong relationship between diabetes on PCOS and abortion.

Inadequate Glucagon Suppression During OGTT in Prediabetes: A Systematic Review and Meta-analysis.

Glucagon plays a role in the development of type 2 diabetes, yet its role in prediabetes (preDM) remains uncertain. To evaluate glucagon levels in the fasting state and its response to glucose inhibition in preDM through meta-analysis. A systematic search across Pubmed, Embase, Web of Science, and Cochrane Library identified studies assessing glucagon levels during 75 g oral glucose tolerance test (OGTT) in both preDM and normal glucose tolerance (NGT) cohorts. Data on glucagon, glucose, and insulin were pooled using a random-effect model. Although glucagon levels decreased in both preDM and NGT groups upon glucose challenge, glucagon levels at 0 hours, 0.5 hours, 1 hour, and 1.5 hours in preDM were significantly higher compared to NGT, despite higher glucose levels at all time points and higher insulin levels at 0 hours, 1 hour, 1.5 hours, and 2 hours during OGTT. Subgroup analysis revealed that in studies using the radioimmunoassay method, glucagon levels in preDM were higher at 0.5 hours and 1 hour than NGT, while in studies using the ELISA method, glucagon levels were similar to those of the NGT group despite higher glucose in preDM compared to NGT. Fasting glucagon level was inadequately suppressed in both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Responsiveness to glucose inhibition was preserved in IFG, while glucagon level in IGT group at 0.5 hours after glucose intake was not suppressed and was higher than NGT. Glucagon was not adequately suppressed during OGTT in preDM. Glucagon dysregulation is a contributing mechanism underlying both IFG and IGT.

Contribution of methamphetamine and insulin to the death of a woman suffering from type I diabetes - which played the greater role?

This report presents a fatal case of a young female Type I diabetic patient who developed convulsions and loss of consciousness after taking methamphetamine and spending some time in a dance club. During the convulsions, she was given sugar and when no response occurred, her boyfriend who was not experienced in the use of insulin administered a dose of insulin to her. The woman lost consciousness and died despite the efforts of the emergency service. A biochemical analysis revealed a high level of insulin (196.67 mU/L) and low levels of glucose (2.96 mmol/L) and C-peptide (26 pmol/L). Toxicological analysis revealed a methamphetamine concentration of 389 ng/mL and an amphetamine concentration of 19 ng/mL. The forensic perspective of the difficult determination of the contribution of each of the factors to the death, i.e., the pre-existing medical condition (Type I diabetes), the use of methamphetamine, the physical exertion at the dance club, and, finally, the non-indicated administration of insulin, is discussed. The ruling of the court is also reported.

Overexpressing the PRSS1 Protein Specifically in the Pancreatic Islets by Nano-Celery Provided Protection against Streptozotocin-Induced Diabetes Mellitus in Male Rat

The goal of this study was to find out how giving whole barley grain to rats that had been given streptozotocin (STZ) affected lipid peroxidation (LPO), the activities of antioxidant enzymes in erythrocytes, and the production of insulin genes in the pancreas. A single shot of STZ (60 mg/kg, i.p.) caused diabetes in the experiment. The oxidative stress was measured by the amount of LPO in the tissue, the amount of reduced glutathione (GSH), and the activities of SOD, CAT, GPx, and GR enzymes in erythrocytes. The most important things that were seen in diabetic control rats were higher blood sugar and LPO levels, lower GSH levels, and lower enzyme functions. When diabetic rats (group G2) were given barley seed whole grain by mouth for 30 days, their LPO level dropped significantly compared to rats that were given STZ (group G3). Furthermore, diabetic rats (group G4) that were fed barley had higher levels of both enzyme- and non-enzymatic antioxidants, as well as higher levels of insulin and regeneration (PRSS1) genes, compared to diabetic normal rats (group G2). The results make it clear that oxidative stress plays a part in causing diabetes and suggest that adding barley to an animal's diet might help protect them.

Insulinoma presenting with anti-insulin antibodies.

An 89-year-old woman presented with a 6-year history of occasional episodes of impaired consciousness that were relieved by ingestion of a snack. Three months before presenting to our hospital, she had been hospitalized in a local hospital with subdural hematoma caused by a head contusion, where previously unrecognized hypoglycemia was discovered. Fasting plasma glucose concentration was 37 mg/dL, with a relatively high serum level of insulin (34.9 µU/mL). Computed tomography showed a 14 mm hyperenhancing tumor in the tail of the pancreas and she was referred to our hospital for further investigation. A prolonged fasting test revealed the plasma glucose concentration reduced to 43 mg/dL (2.4 mmol/L) at 8 h after the last meal. Serum insulin, proinsulin, and C-peptide concentrations were 21.1 µU/mL, 16.9 pmol/L, and 2.72 ng/mL, respectively. Subsequent intravenous administration of 1 mg of glucagon increased the plasma glucose concentration to 76 mg/dL (4.2 mmol/L). Moreover, the insulin-to-C-peptide molar ratio was 0.14. These data indicated the presence of insulinoma. Interestingly, serum anti-insulin antibodies were elevated (21.1 U/mL), although she had no history of taking exogenous insulin injection, alpha lipoic acid, or sulfhydryl group-containing agents. Human leukocyte antigen (HLA) typing revealed HLA-DRB1*0407 and HLA-DRB1*1405 alleles. Treatment with diazoxide prevented hypoglycemia, but was discontinued due to weight gain and leg edema. Elevated serum anti-insulin antibodies persisted almost 1 year after the diagnosis of insulinoma. We present a rare case of insulinoma concomitant with serum anti-insulin antibodies. Insulinoma presenting with concomitant anti-insulin antibodies appears rare. Insulin/C-peptide molar ratio and serum insulin concentration are useful for differentiating insulinoma and autoimmune syndrome. Flash glucose monitoring systems appear suitable for evaluating treatment outcomes.

Myo-inositol rescued insulin resistance and dyslipidemia in db/db mice.

Myo-inositol (MI), present in a variety of foods, is essential in several important processes of cell physiology. In this study, we explored the protective effects of MI against hyperglycemia and dyslipidemia in db/db mice, a typical animal model of type 2 diabetes mellitus (T2DM). MI supplement effectively suppressed the high plasma glucose and insulin levels and markedly relieved the insulin resistance (IR) in the db/db mice, comparable to metformin's effects. In MIN6 pancreatic β cells, MI also restrained the upsurge of insulin secretion stimulated by high-concentration glucose but had no impact on the promoted cell proliferation. Moreover, MI abated the enhanced plasma triglyceride and total cholesterol levels in the db/db mice. Notably, the lipid droplet formation of mesenchymal stem cells (MSCs) from db/db mice was significantly diminished after the treatment of MI, indicating that MI could effectively inhibit the differentiation of db/db mouse MSCs into adipocytes. However, MI regretfully failed to control obesity in db/db mice. This work proved that MI significantly helped db/db mice's metabolic disorders, indicating that MI has potential as an effective adjunctive treatment for hyperglycemia and dyslipidemia in T2DM patients.

Alpha-lipoic acid induced insulin autoimmune antibody syndrome

BackgroundInsulin autoimmune antibody syndrome is an uncommon cause of hypoglycemia in non-diabetic individuals. We report a case of alpha-lipoic acid-induced insulin autoimmune antibody syndrome.Case reportA 40-year-old non-diabetic female presented with unresponsiveness due to severe hypoglycemia. Investigations revealed high fasting insulin levels, elevated C-peptide, and positive anti-insulin antibodies. Further history revealed recent ingestion of alpha-lipoic acid supplements. She was diagnosed with alpha-lipoic acid-induced insulin autoimmune antibody syndrome and managed with symptomatic measures and steroids.ConclusionsThis case highlights the importance of recognizing drug-induced insulin autoimmune antibody syndrome as a potential cause of hypoglycemia in non-diabetic individuals, especially in the context of recent supplement or medication use.

Clustering Identifies Subtypes With Different Phenotypic Characteristics in Women With Polycystic Ovary Syndrome.

Hierarchical clustering (HC) identifies subtypes of polycystic ovary syndrome (PCOS). This work aimed to identify clinically significant subtypes in a PCOS cohort diagnosed with the Rotterdam criteria and to further characterize the distinct subtypes. Clustering was performed using the variables body mass index (BMI), luteinizing hormone (LH), follicle-stimulating hormone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), testosterone, insulin, and glucose. Subtype characterization was performed by analyzing the variables estradiol, androstenedione, dehydroepiandrosterone, cortisol, anti-Müllerian hormone (AMH), total follicle count (TFC), lipid profile, and blood pressure. Study participants were girls and women who attended our university hospital for reproductive endocrinology screening between February 1993 and February 2021. In total, 2502 female participants of European ancestry, aged 13 to 45 years with PCOS (according to the Rotterdam criteria), were included. A subset of these (n = 1067) fulfilled the National Institutes of Health criteria (ovulatory dysfunction and hyperandrogenism). Main outcome measures included the identification of distinct PCOS subtypes using cluster analysis. Additional clinical variables associated with these subtypes were assessed. Metabolic, reproductive, and background PCOS subtypes were identified. In addition to high LH and SHBG levels, the reproductive subtype had the highest TFC and levels of AMH (all P < .001). In addition to high BMI and insulin levels, the metabolic subtype had higher low-density lipoprotein levels and higher systolic and diastolic blood pressure (all P < .001). The background subtype had lower androstenedione levels and features of the other 2 subtypes. Reproductive and metabolic traits not used for subtyping differed significantly in the subtypes. These findings suggest that the subtypes capture distinct PCOS causal pathways.