Caveolin-1 Is Essential for the Improvement of Insulin Sensitivity through AKT Activation during Glargine Treatment on Diabetic Mice

Insulin treatment was confirmed to reduce insulin resistance, but the underlying mechanism remains unknown. Caveolin-1 (Cav-1) is a functional protein of the membrane lipid rafts, known as caveolae, and is widely expressed in mammalian adipose tissue. There is increasing evidence that show the involvement of Cav-1 in the AKT activation, which is responsible for insulin sensitivity. Our aim was to investigate the effect of Cav-1 depletion on insulin sensitivity and AKT activation in glargine-treated type 2 diabetic mice. Mice were exposed to a high-fat diet and subject to intraperitoneal injection of streptozotocin to induce diabetes. Next, glargine was administered to treat T2DM mice for 3 weeks (insulin group). The expression of Cav-1 was then silenced by injecting lentiviral-vectored short hairpin RNA (shRNA) through the tail vein of glargine-treated T2DM mice (CAV1-shRNA group), while scramble virus injection was used as a negative control (Ctrl-shRNA group). The results showed that glargine was able to upregulate the expression of PI3K and activate serine phosphorylation of AKT through the upregulation of Cav-1 expression in paraepididymal adipose tissue of the insulin group. However, glargine treatment could not activate AKT pathway in Cav-1 silenced diabetic mice. These results suggest that Cav-1 is essential for the activation of AKT and improving insulin sensitivity in type 2 diabetic mice during glargine treatment.

To Compare Metformin Vs Insulin in Gestational Diabetes in Terms of Neonatal Hypoglycemia

Aim: To compare metformin vs insulin in Gestational Diabetes in terms of neonatal hypoglycemia. Methodology: Study design: Randomized controlled trial Setting: Obstetrics / Gynecology Unit-l, Holy Family Hospital, Rawalpindi. Duration of study: 6 months i.e. 10-11-2017 to 10-05-2018 Data collection procedure: 240 patients were randomly allotted into two groups; A & B. Group A received metformin and group B received regular insulin. Patient was admitted at 36 wks onwards. Neonatal hypoglycemia was measured and entered in structured Performa. All the data was entered and analyzed through SPSS version 22. Results: In this study, the mean ± sd ages of patients were 28.7±5.05 years in insulin group while 28.01±4.37years in metformin group. Mean neonatal blood sugar level was 51.58±11.77mg/dl in insulin group while 57.37±10.61mg/dl in metformin group. The difference was significant (p<0.05). In this study, neonatal hypoglycemia was noted in 28 (23.3%) cases with insulin while in 1 (0.8%) case with metformin. The difference was significant (p<0.05). Conclusion: Metformin has better outcome than insulin in terms of less number of neonatal hypoglycemia. Key words: Gestational Diabetes, Metformin, Insulin, Neonatal Hypoglycemia

Type I Diabetes Mellitus and Insulin Therapy on Bone Microarchitecture, Composition and Mechanical Properties

Background: The aim of this study was to evaluate the microarchitecture, composition and mechanical properties of cortical bone of rats with type I diabetes mellitus (TIDM) and submitted to insulin therapy (IT). Methods: Thirty rats were divided into three groups (n=10): non-diabetic, diabetic and diabetic+insulin. TIDM was induced by intravenous injection of streptozotocin. In diabetic+insulin group, 4IU insulin was administered twice per day (1IU at 7am and 3IU at 7pm). The animals were euthanized five weeks after TIDM induction; the tibiae were removed and submitted to microcomputed tomography (micro-CT, 8µm), fourier transform infrared spectroscopy (FTIR) and dynamic microhardness indentation. Results: Micro-CT analysis showed that diabetic group had lower bone surface/tissue volume ratio (BS/BV) (p=0.018), cortical thickness (Ct.Th) (p<0.001) and degree of anisotropy (Ct.DA) (p=0.034) values compared to non-diabetic group. The diabetic group showed lower Ct.Th than diabetic + insulin group (p=0.018). The non-diabetic group had lower fractal dimension (Ct.FD) values compared to diabetic groups (p<0.001). The ATR-FTIR analyses showed lower values for all measured parameters in the diabetic group than non-diabetic group (amide I ratio: p=0.046; crystallinity index: p=0.038; matrix:mineral ratios - M:MI: p=0.006; M:MIII: p=0.028). The diabetic+insulin group showed a lower crystallinity index (p=0.022) and M:MI ratio (p=0.002) than non-diabetic and diabetic groups, respectively. The diabetic group showed lower Vickers hardness values than non-diabetic (p<0.001) and diabetic+insulin (p=0.003) groups. Conclusion: TIDM negatively affect bone microarchitecture, collagen maturation, mineralization and bone microhardness. Moreover, insulin minimized the effect of TIDM on cortical thickness and organic/mineral matrix.

Glycemic control and neonatal outcomes in women with gestational diabetes mellitus treated using glyburide, metformin, or insulin: a pairwise and network meta-analysis

Aims We aimed to assess the comparative efficiency and safety of the use of glyburide, metformin, and insulin in gestational diabetes mellitus (GDM). Methods We searched for randomized controlled trials that compared glyburide, metformin, and insulin in GDM. Data regarding glycemic control and neonatal safety were collected and analyzed in pairwise and network meta-analyses. Results A total of 4533 individuals from 23 trials were included. Compared with glyburide, metformin reduced 2-h postprandial blood glucose (2HPG) to a greater extent (standard mean difference (SMD) 0.18; 95% credible interval (CI) 0.01, 0.34). There were significantly lower prevalence of neonatal hypoglycemia (risk difference (RD) − 0.07; 95%CI − 0.11, − 0.02) and preeclampsia (RD − 0.03; 95%CI − 0.06, 0) in the metformin group than in the insulin group. The metformin group had significantly lower birth weight (SMD − 0.17; 95%CI − 0.25, − 0.08) and maternal weight gain (SMD − 0.61; 95%CI − 0.86,− 0.35) compared with the insulin group. Network meta-analysis suggested that metformin had the highest probability of successfully controlling glycemia and preventing neonatal complications. Conclusions The present meta-analysis suggests that metformin may be as effective as insulin for glycemic control and is the most promising drug for the prevention of neonatal and maternal complications.

Effects of insulin on sperm cell quality in ram semen cooled at 5°C

Insulin is present in the seminal plasma and is involved in sperm activities like motility and capacitation. However, the effects of insulin on the viability of cooled ram sperm are not fully understood. Therefore, the objective of the current study was to evaluate the effect of insulin addition on ram sperm maintained at 5ºC. Sperm samples were collected from six healthy, mature Santa Inês rams. The ejaculates were divided into two aliquots with (insulin group) or without (control group) insulin (3 IU mL-1) in the semen extender, and then cooled at 5°C for 48 hours. Subsequently, the sperm cells were evaluated for motility and kinetics using computer-assisted semen analysis. The samples were evaluated for acrosomal integrity by fluorescein using isothiocyanate combined with peanut agglutinin (FITC-PNA) and membrane functionality by the hypoosmotic swelling test. The semen analysis was performed after 24 or 48 hours of cooling. There was an increased percentage of progressive sperm motility (%), straightness (%), linearity (%) and beat caudal frequency (Hz) in the insulin group after 24 and 48 hours of cooling (p < 0.05). However, insulin did not affect total sperm motility, sperm velocities (VSL, VAP and VCL) (μm seg-1), acrosomal integrity and membrane functionality during cooling (p > 0.05). In conclusion, the addition of 3 IU mL-1 insulin to ram semen extender improved the quality of sperm motility after cooling.

Relation between Different Types of Treatment and Glycemic Control in Diabetic Pregnant Women

Gestational diabetes mellitus (GDM) is a common medical condition associated with pregnancy. GDM is defined as hyperglycemia that is diagnosed during pregnancy and is not clearly overt diabetes that existed prior to pregnancy. The sample of the study was sixty diabetic pregnant women who came for follow up at obstetrics and gynecology department in TMC in Tripoli medical center during the year 2016. The patients divided according to the type of treatments they received into three groups; A: Patients who took Oral hypoglycemic agents (OHA), B: Patients who took insulin, C: Patents who took both drugs (OHA and insulin), Glycemic control was assessed using HBA1c level, FBS and RBS. This study shows that about 70% of the patients who took OHA had type 1 diabetes and 30% had type 2 diabetes. About 77.8% of patients who took insulin had type 2 diabetes and 22.2% had type 1 diabetes. And 73.2% of the patients who were treated with the combination of drugs had type 2 diabetes and 26.8% had type 1 diabetes. The current study demonstrates that 80% of patients who took OHA had good control, 33.3% of patients who took insulin had good control and 53.7% of patients who took both drugs had good control. Regarding the fasting blood sugar of the patients, the result illustrates the following; High level was reported in 20% of OHA group, 33.3% of insulin group and 31.7% of both drugs group. On the birth weight, the macrosomia (>4kg) was more in insulin group (33.3%) than other groups (10% of OHA and 31.7% of both drugs group). GDM is a condition that should be treated and prevented, as uncontrolled GDM can affect the mother and the fetal growth.

Clinical and radiographic variables related to implants with simultaneous grafts among type 2 diabetic patients treated with different hypoglycemic medications: a retrospective study

Background The influence of different hypoglycemic agents on peri-implant variables among type 2 diabetes mellitus patients is still unclear. Therefore, the aim of this study was to assess the radiographic marginal bone loss and clinical parameters around implants in patients using different hypoglycemic agents. Methods In this retrospective cohort study, the dental implant records of type 2 diabetes mellitus patients who met the inclusion criteria were collected. The patients using only single medication as follows: insulin, metformin, or glucagon-like peptide-1 (GLP-1) drugs, were grouped according to their medication. These patients received implant placement with the same initial status, and all the prosthesis restorations were cement-retained ceramic crowns. The peri-implant marginal bone levels were evaluated by periapical radiographs immediately after implant placement and at 1 and 2-year follow-up visits. The baseline characteristics were compared among groups. The peri-implant radiographic marginal bone loss and clinical parameters were preliminarily compared using the Kruskal–Wallis test, and then the covariates were controlled by covariance analysis. Bonferroni post hoc adjustment test was performed for the multiple comparisons. Results After a review of more than 7000 medical records, a total of 150 patients with 308 implants at 1-year follow-up were assessed. The peri-implant marginal bone loss in the GLP-1 drug group was significantly smaller than the insulin group and metformin group (P < 0.01). The radiographic bone loss in the metformin group was higher than the insulin group (P < 0.05). Some of these included patients were lost to follow-up. Only 74 patients with 129 implants completed the 2-year follow-up. The radiographic bone loss in the metformin group was still higher than the insulin group (P < 0.05) and GLP-1 group (P < 0.01). There was no significant difference in the BOP (+) and the mean PD among groups (P > 0.05). Conclusions The radiographic variables were not exactly the same among the patients with different hypoglycemic agents at both the 1 and 2-year follow-ups. After ensuring consistency in baseline characteristics, the positive effect of GLP-1 drugs on peri-implant bone remodeling may be no less than insulin or metformin. More studies are needed to verify the direct effect of these drugs on peri-implant bone. Clinical trial registration number ChiCTR2000034211 (retrospectively registered).

Impact of Hyperinsulinemia on Long-Term Clinical Outcomes of Percutaneous Coronary Intervention in Non-Diabetes Patients With Acute Myocardial Syndrome.

Background and Objectives: Hyperinsulinemia plays a key role in development of cardiovascular impairment in patients with Metabolic syndrome. The aim of this study was to evaluate the influence of hyperinsulinemia on long-term Clinical outcomes of percutaneous coronary intervention (PCI) in patients with acute myocardial syndrome. Methods: Between March 2016 and January 2019, patients of ACS without diabetes mellitus and received primary PCI were enrolled. 368 patients were divided into low insulin group (n=157), medium insulin group (n=154) and high insulin group (n=157) according to tertiles of fasting insulin (FINS) level. The primary endpoint was major adverse cardiac events (MACE; all-cause death, non-fatal myocardial infarction, target vessel revascularization (TVR)) at 24 months. Second endpoint was angina-hospitalization. Results: High insulin group had an unfavorable prognosis, with higher rate of MACE (34.39%) compared with low insulin group (22.29%) and medium insulin group (23.37%) at 24 months (P<0.05). This difference was mainly driven by the increase of TVR. High insulin group also had higher rate of angina-hospitalization than low insulin group. Multivariate logistic regression showed that high insulin level (OR2.636, 95%CI 1.378-5.023), small vessel lesion (OR2.636, 95%CI 1.378-5.023), bifurcation lesion (OR3.506, 95%CI 1.048-11.922) and Syntax score(OR1.116, 95%CI 1.054-1.182) were independent predictors of MACE in ACS patients after PCIConclusion: Hyperinsulinemia might be a valid predictor of clinical outcomes in ACS patients undergoing PCI.

Neonatal outcomes in case of euglycemic control in gestational diabetes using insulin versus metformin. Randomized controlled trial

Background: Gestational diabetes mellitus (GDM) is a major global public health issue, with prevalence increasing in recent years due to the epidemic of obesity and type 2 diabetes. Aim of the Work: to compare different neonatal outcomes according to the different treatment modalities used in the management of GDM. Our hypothesis was that Metformin is as effective and safe as insulin in patients with gestational diabetes. Patients and Methods: The current non inferiority-Randomized controlled trial was conducted at Ain Shams Maternity hospital between June 2020 to February 2021. The study included 140 outpatient cases or admitted patients for antenatal care: Group A: women were given Metformin (Total 70) and Group B: Women were given insulin. (Total 70). Results: there was no significant difference between Metformin and Insulin groups regarding age, enrollment BMI, parity and family history of DM. There was no significant difference between Metformin and Insulin groups regarding gestational age at enrollment and delivery as well as pregnancy duration after intervention. BMI at delivery, BMI increase as well as BMI increase rate were significantly lower in Metformin group. There were no significant differences between Metformin and Insulin groups regarding fasting, two-hour postprandial and HbA1c blood glucose at enrollment and throughout treatment as well as their reduction after intervention. Maternal complications as hypoglycemia, hyperglycemia and preeclampsia were non-significantly less frequent among Metformin group than among Insulin group. Compliance to treatment was significantly more frequent among Metformin group than among Insulin group. Cesarean delivery was non­significantly less frequent among Metformin group than among Insulin group. There was no significant difference between Metformin and Insulin regarding birth weight APGAR-1, but APGAR-5 was significantly higher in Metformin group. Neonatal complications as IUFD, IUGR, macrosomia, congenital anomalies, neonatal hypoglycemia, respiratory distress and NICU admission were non-significantly less frequent among Metformin group. Conclusions: From the results of current study we can conclude that: Oral metformin was effective as insulin injection in control and management of GDM. BMI was controlled with oral metformin better than insulin injection. Maternal and neonatal complications specially birth weight were the same with both types of treatment. Women had better compliance to metformin treatment. Type of delivery wasn’t affected by type of treatment.

Exhaustive endurance exercise activates brain glycogen breakdown and lactate production more than insulin-induced hypoglycemia

Brain glycogen localized in astrocytes produces lactate via cAMP signaling, which regulates memory functions and endurance capacity. Exhaustive endurance exercise with hypoglycemia decreases brain glycogen, although the mechanism underlying this phenomenon remains unclear. Since insulin-induced hypoglycemia decreases brain glycogen, this study tested the hypothesis that hypoglycemia mediates exercise-induced brain glycogen decrease. To test the hypothesis, the effects of insulin- and exhaustive exercise-induced hypoglycemia on brain glycogen levels were compared using the microwave irradiation method in adult Wistar rats. The insulin challenge and exhaustive exercise induced similar levels of severe hypoglycemia. Glycogen in the hypothalamus and cerebellum decreased similarly with the insulin challenge and exhaustive exercise; however, glycogen in the cortex, hippocampus, and brainstem of the exercise group were lower compared to the insulin group. Blood glucose correlated positively with brain glycogen, but the slope of regression lines was greater in the exercise group compared to the insulin group in the cortex, hippocampus, and brainstem, but not the hypothalamus and cerebellum. Brain lactate and cAMP levels in the hypothalamus and cerebellum increased similarly with the insulin challenge and exhaustive exercise, but those in the cortex, hippocampus, and brainstem of the exercise group were higher compared to the insulin group. These findings support the hypothesis that hypoglycemia mediates the exercise-induced reduction in brain glycogen, at least in the hypothalamus and cerebellum. However, glycogen reduction during exhaustive endurance exercise in the cortex, hippocampus, and brainstem is not due to hypoglycemia alone, implicating the role of exercise-specific neuronal activity in brain glycogen decrease.