P704Nanoliposomal anti-PCSK9 vaccine ameliorates glucose intolerance and insulin resistance in diabetic rats

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A A Momtazi-Borojeni ◽  
M R Jaafari ◽  
E Abdollahi ◽  
M Banach ◽  
A Sahebkar
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Tolerance Test ◽  
Diabetic Rats ◽  
Pcsk9 Inhibitors ◽  
Insulin Tolerance ◽  
Pcsk9 Inhibition ◽  
Histopathology Examination

Abstract Background PCSK9 inhibitors have emerged as an effective lipid-lowering approach. Although the results of available studies suggest a positive association of plasma PCSK9 levels with glycemic parameters and risk of DM, the effects of PCSK9 inhibitors on glucose intolerance and insulin resistance as the key features of DM remain unclear. Purpose The present study was directed to determine effect of vaccine-mediated PCSK9 inhibition on glucose intolerance and insulin resistance in experimental diabetic rats. Methods Nanoliposomal vaccine composing from PCSK9-linked nanoliposome particles mixed in Alum adjuvant was subcutaneously injected four times with bi-weekly intervals in Wistar-Albino rats. Two weeks after the last immunization, vaccinated and non-vaccinated rats were subjected to diabetes experiment induced by single intraperitoneal injection of streptozotocin (STZ). One week after STZ injection, glucose tolerance ability of each animal was evaluated by using oral glucose tolerance test (OGTT) on the overnight fasted rats with glucose dose at 2 g/kg. Two weeks after STZ injection, insulin tolerance test (ITT) viaintraperitoneal injection of insulin (0.8 U/kg) was performed to determine the measure of peripheral utilization of glucose. The plasma concentrations of total cholesterol (TC), LDL-C, HDL-C, and TG were measured. Results Nanoliposomal vaccine exposing PCSK9 peptide was found to provoke high-titers IgG antibody response against PCSK9 in rats, which was associated with the decrease plasma levels and function of plasma PCSK9. During the first week after STZ injection, it was indicated that the fasting blood glucose (FBG) level was 49% (−171.7±35 mg/dL, p<0.0001) lower in the vaccinated diabetic (VD) rats, when compared to the diabetic control (DC) rats. OGTT assessment revealed that the VS rats had significantly improved glucose tolerance ability and recorded significant reduction in the level of blood glucose over the period of 180 min, when compared with the DC rats. Measurement of integrated areas under the glucose curve values demonstrated that blood glucose levels were significantly (p<0.0001) decreased by 34.5% in the VS rats than the DC rats. In addition, ITT analysis showed that after insulin administration blood glucose level was decreased by 49.3% in the VS group compared with the DC group. The VS rats showed significantly lower (−26.65%, p=0.02) plasma LDL-C levels than the DC rats (Figure). Histopathology examination indicated that the pancreatic islet of the VS rats had a slightly decreased population of β-cells and few α-cells. Histopathology examination of the liver tissues of both VS and DC rats exhibited the normal histology with the normal hepatic architecture composed of hepatic lobules with normal central vein. Conclusions PCSK9 inhibition using liposomal vaccine can protect from glucose and insulin tolerance impairments in diabetic rats through an unknown and pancreatic-independent mechanism.

scholarly journals Pharmacological potential of methanol extract of Anacardium occidentale stem bark on alloxan-induced diabetic rats

2018 ◽  
Vol 5 (7) ◽  
pp. 2440-2454
Author(s):  
D. A. Omoboyowa ◽  
F. O. Afolabi ◽  
T. C. Aribigbola
Keyword(s):  
Blood Glucose ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Methanol Extract ◽  
Stem Bark ◽  
Tolerance Test ◽  
Diabetic Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cells

Background: The anti-hyperglycemic potential of methanol stem bark extract of Anacardium occidentale (MSBEAO) was investigated using an alloxan-induced diabetic rat model. Alloxan administration induces the generation of free radicals which can affect antioxidant status resulting in the disruption of the β-cells of the pancreas. Therefore, this study examines the antioxidant potential of the plant extract and the ameliorating effect on the pancreas of alloxan-induced diabetic rats. Methods: Diabetes was induced by intraperitoneal injection of 150 mg/kg body weight of alloxan monohydrate. MSBEAO, at a concentration of 100 or 200 mg/kg b.w. was orally administered to alloxan-induced diabetic rats and normal rats. The hypoglycemic effect, oral glucose tolerance test, and biochemical assay of alloxan-induced diabetic rats were assayed using standard procedures. Results: Preliminary phytochemical screening of the extract revealed the presence of alkaloids, tannins, saponins, terpenoids, carbohydrates, and phenols at moderate concentrations. The lethality dose (LD50) of the plant extract was found to be equal to or less than 5000 mg/kg b.w. The hypoglycemic effect of the extract on the non-diabetic rats revealed a significant (p<0.05) decrease in the blood glucose concentration of animals administered with 1 g/kg b.w. of the extract, compared to normal control rats administered with normal saline. In the oral glucose tolerance test, the methanol extract exerted the highest response, similar to glibenclamide after 15 and 30 minutes of administration, compared to the control rats. The methanol extract yielded the highest blood glucose lowering effects after 9 days of treatment (p<0.05), compared to diabetic rats administered with normal saline and 0.3 mg/kg b.w. of glibenclamide. Administration of the extract at 200 mg/kg b.w. showed improved pancreas architecture and regeneration of the β-cells, compared with the pancreas of animals in the other groups. Conclusion: The results of this study suggest that MSBEAO is a potentially effective agent for the management of diabetes which might result from the antioxidant-generating capacity of the stem bark.

scholarly journals Hypoglycemic effects and mechanisms of electroacupuncture on insulin resistance

2014 ◽  
Vol 307 (3) ◽  
pp. R332-R339 ◽  
Author(s):  
Jieyun Yin ◽  
Jian Kuang ◽  
Manisha Chandalia ◽  
Demidmaa Tuvdendorj ◽  
Batbayar Tumurbaatar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Free Fatty Acid ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
High Fat

The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on blood glucose and insulin sensitivity in mice fed a high-fat diet. Both wild-type (WT) and adipose ectonucleotide pyrophosphate phosphodiesterase (ENPP1) transgenic (TG) mice were fed a high-fat diet for 12 wk; for each mouse, an intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed with or without EA at abdomen or auricular areas. A high-fat diet-induced insulin resistance in both WT and TG mice. In the WT mice, EA at 3 Hz and 15 Hz, but not at 1 Hz or 100 Hz, via CV4+CV12 significantly reduced postprandial glucose levels; EA at 3 Hz was most potent. The glucose level was reduced by 61.7% at 60 min and 74.5% at 120 min with EA at 3 Hz (all P < 0.001 vs. control). Similar hypoglycemic effect was noted in the TG mice. On the contrary, EA at auricular points increased postprandial glucose level ( P < 0.03). 4). EA at 3 Hz via CV4+CV12 significantly enhanced the decrease of blood glucose after insulin injection, suggesting improvement of insulin sensitivity. Plasma free fatty acid was significantly suppressed by 42.5% at 15 min and 50.8% at 30 min with EA ( P < 0.01) in both WT and TG mice. EA improves glucose tolerance in both WT and TG mice fed a high-fat diet, and the effect is associated with stimulation parameters and acupoints and is probably attributed to the reduction of free fatty acid.

Insulin resistance caused by amylin in conscious rats is independent of induced hypocalcemia and fades during long-term exposure

1993 ◽  
Vol 129 (4) ◽  
pp. 360-365 ◽  
Author(s):  
Clemens Fürnsinn ◽  
Peter Nowotny ◽  
Michael Roden ◽  
Madeleine Rohac ◽  
Thomas Pieber ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Tolerance Test ◽  
Zucker Rats ◽  
Control Group ◽  
Short Term ◽  
Euglycemic Hyperinsulinemic Clamp

To compare the effect of short- vs long-term amylin infusion on insulin sensitivity, glucose tolerance and serum calcemia, euglycemic-hyperinsulinemic clamp (26 pmol·kg−1·min−1) and glucose tolerance tests (2.4 mmol/kg over 30 min) were performed in lean Zucker rats. Three infusion protocols were employed: control group: 24 h of iv saline; short-term amylin exposure: 22 h of iv saline followed by 2 h of iv amylin (20 μg/h); long-term amylin exposure: 24 h of iv amylin (20 μg/h). Insulin resistance was induced by short-term amylin infusion during euglycemic clamping, as shown by a 41% decrease in space-corrected glucose infusion rates (μmol·kg−1·min−1; control group, 106.0±15.0; short-term iv amylin, 62.7±15.0; p<0.00 5). After long-term amylin exposure, insulin sensitivity was identical to control values (109.9±6.7). This fading action of amylin was confirmed by data from the glucose tolerance test, demonstrating glucose intolerance after short- but not after long-term amylin exposure. Serum calcium concentration decreased during short-term (2 h) amylin infusion (from 2.52±0.15 to 2.09±0.12 mmol/l; p<0.01) and hypocalcemia of a similar extent also was present after 22 h and 24 h of amylin exposure (2.10±0.09 and 2.04±0.14 mmol/l, respectively). The data demonstrate that short-term amylin infusion induces insulin resistance and glucose intolerance, both of which vanish during long-term (>22 h) amylin exposure, being apparently independent of induced hypocalcemia.

scholarly journals Lactobacillus rhamnosus Reduces Blood Glucose Level through Downregulation of Gluconeogenesis Gene Expression in Streptozotocin-Induced Diabetic Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Eko Farida ◽  
Lilis Nuraida ◽  
Puspo E. Giriwono ◽  
Betty S. L. Jenie
Keyword(s):  
Blood Glucose ◽  
Glucose Tolerance ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Fasting Blood Glucose ◽  
Lactobacillus Rhamnosus ◽  
Tolerance Test ◽  
Diabetic Rats ◽  
The Body ◽  
Oral Glucose

Some lactic acid bacteria (LAB) are observed to be potential probiotics with functional properties such as lowering fasting blood glucose (FBG), as a promising hyperglycemia management. This study investigated the ability and mechanism of Lactobacillus rhamnosus BSL and Lactobacillus rhamnosus R23 on lowering FBG in diabetic rats induced by streptozotocin (STZ). The rats were orally administered with L. rhamnosus BSL and L. rhamnosus R23 by giving 1 mL cell suspension (109 CFU/mL) daily for 30 days. The body weight (BW) was recorded once in three days, and FBG was recorded once in six days. An oral glucose tolerance test (OGTT) was measured 1 week after injection with STZ and before sacrifice. Fecal samples were collected on days 0, 15, and 30 for LAB population and identification, performed by PCR detecting 16S rRNA. Oral administration of L. rhamnosus BSL and L. rhamnosus R23 decreased FBG and improved glucose tolerance via downregulation of glucose-6-phosphatase (G6pc) expression by 0.57- and 0.60-fold change, respectively (P<0.05). The lipid profiles, BUN, creatinine, SGOT, and SGPT were significantly (P<0.05) different between normal and diabetic rats, but they were not significantly (P>0.05) different among diabetic rats. Both strains were effective in increasing fecal LAB population. Molecular identification of the isolated LAB from fecal sample indicated that they were able to survive and pass through the digestive tract. These results suggested that both strains have the ability to manage blood glucose level and become a promising agent to manage hyperglycemia and diabetes.

scholarly journals Saturated- and n-6 Polyunsaturated-Fat Diets Each Induce Ceramide Accumulation in Mouse Skeletal Muscle: Reversal and Improvement of Glucose Tolerance by Lipid Metabolism Inhibitors

Endocrinology ◽  
2010 ◽  
Vol 151 (9) ◽  
pp. 4187-4196 ◽  
Author(s):  
G. Frangioudakis ◽  
J. Garrard ◽  
K. Raddatz ◽  
J. L. Nadler ◽  
T. W. Mitchell ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
De Novo ◽  
Saturated Fat ◽  
Tolerance Test ◽  
Polyunsaturated Fat ◽  
Unsaturated Fat ◽  
Fat Diets

Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg · d), or MYR (0.3 mg/kg · d) were administered by mini-pumps in the final 4 wk. Glucose homeostasis was examined by glucose tolerance test. Muscle ceramide and PA were analyzed by mass spectrometry. Expression of LASS isoforms (ceramide synthases) was evaluated by immunoblotting. Both saturated and polyunsaturated fat diets increased muscle ceramide and induced glucose intolerance. MYR and LSF reduced ceramide levels in saturated and unsaturated fat-fed mice. Both inhibitors also improved glucose tolerance in unsaturated fat-fed mice, but only LSF was effective in saturated fat-fed mice. The discrepancy between ceramide and glucose tolerance suggests these improvements may not be related directly to changes in muscle ceramide and may involve other insulin-responsive tissues. Changes in the expression of LASS1 were, however, inversely correlated with alterations in glucose tolerance. The demonstration that LSF can ameliorate glucose intolerance in vivo independent of the dietary FA type indicates it may be a novel intervention for the treatment of insulin resistance.

scholarly journals Glucose Intolerance, Insulin Resistance, and Hyperandrogenemia in First Degree Relatives of Women with Polycystic Ovary Syndrome

2003 ◽  
Vol 88 (5) ◽  
pp. 2031-2036 ◽  
Author(s):  
Bülent O. Yildiz ◽  
Hakan Yarali ◽  
Havva Oguz ◽  
Miyase Bayraktar
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Matched Control ◽  
Polycystic Ovary ◽  
Family Members ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Ovary Syndrome ◽  
First Degree Relatives

Polycystic ovary syndrome (PCOS) is associated with hyperinsulinemia, insulin resistance (IR), increased risk of glucose intolerance, and type 2 diabetes. Family studies have indicated a genetic susceptibility to PCOS. The aims of this study were 1) to assess glucose tolerance status, gonadotropins, and androgens in first degree relatives of patients with PCOS; and 2) to assess IR in normal glucose tolerant (NGT) family members. One hundred two family members of 52 patients with PCOS [MothersPCOS (n = 34; mean age, 46.5 yr; mean body mass index (BMI), 28.8 kg/m2), FathersPCOS (n = 24; mean age, 50.4 yr; mean BMI, 27.5 kg/m2), SistersPCOS (n = 19; mean age, 25.1 yr; mean BMI, 22.9 kg/m2), and BrothersPCOS (n = 25; mean age, 23.7 yr; mean BMI, 22.5 kg/m2)] and 82 unrelated healthy control subjects without a family history of diabetes or PCOS (4 age- and weight-matched subgroups, i.e. ControlMothersPCOS, ControlFathersPCOS, ControlSistersPCOS, and ControlBrothersPCOS) were studied. Glucose and insulin (at baseline and during a 75-g, 2-h oral glucose tolerance test) were measured. IR was assessed by fasting insulin (FI), fasting glucose to insulin ratio (FGI), homeostatic model assessment (HOMA IR), and area under the curve for insulin during the oral glucose tolerance test (AUCinsulin) in NGT MothersPCOS, FathersPCOS, SistersPCOS, BrothersPCOS, and matched control subgroups. Including the prestudy-diagnosed 3 mothers and 2 fathers with diabetes, diabetes and impaired glucose tolerance (IGT) were noted in 16% and 30% of MothersPCOS and 27% and 31% of FathersPCOS, respectively. There was no diabetes in SistersPCOS and BrothersPCOS. IGT was found in 5% of SistersPCOS. Impaired fasting glucose was found in 3% of MothersPCOS and 4% of BrothersPCOS. The analysis of NGT family members showed that MothersPCOS had higher FI (P &lt; 0.05), HOMA IR (P &lt; 0.05), and AUCinsulin (P &lt; 0.01) and lower FGI (P &lt; 0.05) than ControlMothersPCOS, whereas all IR parameters were comparable between FathersPCOS and their matched control subgroup. SistersPCOS had higher FI (P &lt; 0.05), HOMA IR (P &lt; 0.01), and AUCinsulin (P &lt; 0.05) and lower FGI (P &lt; 0.01), and BrothersPCOS had higher AUCinsulin (P &lt; 0.01) than their matched control subgroups, respectively. MothersPCOS had higher testosterone levels than ControlMothersPCOS (P &lt; 0.01 and P &lt; 0.05 for pre- and postmenopausal women, respectively). SistersPCOS had higher LH (P &lt; 0.01), testosterone (P &lt; 0.001), androstenedione (P &lt; 0.01), and dehydroepiandrosterone sulfate (P &lt; 0.05) levels than ControlSistersPCOS. There was no difference in gonadotropin and androgen levels in FathersPCOS compared with ControlFathersPCOS or in BrothersPCOS compared with ControlBrothersPCOS. Our results suggest that 1) first degree relatives of patients with PCOS may be at high risk for diabetes and glucose intolerance; 2) NGT female family members have insulin resistance; and 3) mothers and sisters of PCOS patients have higher androgen levels than control subjects. We propose that the high risks of these impairments warrant screening in first degree relatives of patients with PCOS.

scholarly journals Hepatic deletion of p110α and p85α results in insulin resistance despite sustained IRS1-associated phosphatidylinositol kinase activity

F1000Research ◽  
2018 ◽  
Vol 6 ◽  
pp. 1600
Author(s):  
Aditi Chaudhari ◽  
Katarina Ejeskär ◽  
Yvonne Wettergren ◽  
C. Ronald Kahn ◽  
Victoria Rotter Sopasakis
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Insulin Signaling ◽  
Kinase Activity ◽  
Tolerance Test ◽  
Metabolic Phenotype ◽  
Insulin Signal ◽  
Phosphatidylinositol Kinase ◽  
Insulin Tolerance

Background: Class IA phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) is an integral mediator of insulin signaling. The p110 catalytic and p85 regulatory subunits of PI3K are the products of separate genes, and while they come together to make the active heterodimer, they have opposing roles in insulin signaling and action. Deletion of hepatic p110α results in an impaired insulin signal and severe insulin resistance, whereas deletion of hepatic p85α results in improved insulin sensitivity due to sustained levels of phosphatidylinositol (3,4,5)-trisphosphate. Here, we created mice with combined hepatic deletion of p110α and p85α (L-DKO) to study the impact on insulin signaling and whole body glucose homeostasis. Methods: Six-week old male flox control and L-DKO mice were studied over a period of 18 weeks, during which weight and glucose levels were monitored, and glucose tolerance tests, insulin tolerance test and pyruvate tolerance test were performed. Fasting insulin, insulin signaling mediators, PI3K activity and insulin receptor substrate (IRS)1-associated phosphatidylinositol kinase activity were examined at 10 weeks. Liver, muscle and white adipose tissue weight was recorded at 10 weeks and 25 weeks. Results: The L-DKO mice showed a blunted insulin signal downstream of PI3K, developed markedly impaired glucose tolerance, hyperinsulinemia and had decreased liver and adipose tissue weights. Surprisingly, however, these mice displayed normal hepatic glucose production, normal insulin tolerance, and intact IRS1-associated phosphatidylinositol kinase activity without compensatory upregulated signaling of other classes of PI3K. Conclusions: The data demonstrate an unexpectedly overall mild metabolic phenotype of the L-DKO mice, suggesting that lipid kinases other than PI3Ks might partially compensate for the loss of p110α/p85α by signaling through other nodes than Akt/Protein Kinase B.

The Anti-Diabetic and Anti-Hyperlipidemia effect of Citrus maxima Fruit Peel extract in Streptozotocin - Induced Diabetic Rats

2021 ◽  
pp. 5355-5358
Author(s):  
Shaimaa M. Mohammed ◽  
Afnan E. Abd-Almonuim ◽  
Ahmed Majeed ◽  
Haithm Khlaf
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Diabetic Rats ◽  
Antidiabetic Activity ◽  
Fruit Peel ◽  
Blood Samples ◽  
Citrus Maxima

The ethanol extract of Citrus maxima fruit peel was evaluated for its hypoglycaemic and hypolipidemic activity in normal and Streptozotocin (STZ)-induced diabetic rats, using fasting and glucose tolerance test measurements. Experiments were performed using Thirty-Two Male Wister albino rats randomly divided into 4 groups and each group have 8 animals. Group1 assigned as a control injected with normal saline only. Group 2 assigned as a diabetic control injected with Streptozotocin 50mg/Kg, Group 3 assigned for diabetic + Citrus maxima in a dose of 400mg/Kg, Group 4 is assigned for the diabetic + Citrus maxima in a dose of 600mg/Kg. The Streptozotocin is injected intraperitonially to all animal in the groups except the control group. Blood samples were collected from animal before and at 21th day end of the study period. Body weight, blood glucose, serum total cholesterol (TC), triglyceride (TG), and HDL cholesterol were analysed using diagnostic kits. Serum was separated from blood samples collected. In addition oral glucose tolerance test was performed in overnight fasted control animals. Results showed that Citrus maxima extract possesses significant antidiabetic activity against streptozotocin induced diabetic rats by decreasing blood glucose levels, maintaining body weight, and serum lipid concentrations to approximate normal level. Furthermore, the extract of the title plant possesses dose dependent antidiabetic activity.

Abstract P337: Association of Glucose Intolerance and Insulin Resistance with Incident Cardiovascular Disease in a Japanese Urban Cohort: The Suita Study

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Yoshihiro Kokubo ◽  
Makoto Watanabe ◽  
Aya Higashiyama ◽  
Yoko M Nakao ◽  
Takashi Kobayashi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Glucose Tolerance ◽  
Cerebral Infarction ◽  
Glucose Intolerance ◽  
Fasting Glucose ◽  
Tolerance Test ◽  
Normal Glucose Tolerance ◽  
Oral Glucose ◽  
Glucose Levels

Introduction: Glucose intolerance and insulin resistance are known risk factors for cardiovascular disease (CVD). However, few prospective studies were reported the association between combinations of these two factors and incident CVD. We assessed the hypothesis that insulin resistance increased the association between glucose intolerance and CVD in Japanese general population. Methods: We studied 4,638 Japanese individuals (mean age 56.1 years, without CVD) who completed a baseline medical examination and a 75g oral glucose tolerance test in the Suita Study. Glucose categories were defined as follows: diabetes mellitus (DM; fasting plasma glucose levels [FPG] ≥126 mg/dL, 2 hours post-loaded glucose levels [2h-PG] ≥ 200 mg/dL, and/or DM medication); impaired glucose tolerance (IGT; FPG <126 mg/dL and 2h-PG =140-199 mg/dL); impaired fasting glucose (IFG; FPG =100-125 mg/dL and 2h-PG <140 mg/dL); and normal glucose tolerance [NGT]. Insulin resistance was the following formula: HOMA-IR = [FPG] x [fasting insulin] / 405. Insulin resistance was defined as HOMA-IR ≥2.5. Multivariable-adjusted Cox proportional hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated after adjusting for age, sex, body mass index, blood pressure category, hyperlipidemia, smoking, and drinking at the baseline. Results: During the 11.7-year follow-up, we documented 127 cerebral infarctions, 63 hemorrhagic stroke, 12 unclassified strokes, and 143 coronary heart disease events. The adjusted HRs (95% CIs) of subjects with FPG =100-125 mg/dL and ≥126 mg/dL were 1.38 (1.01-1.89) and 2.00 (1.12-3.58) for stroke and 1.47 (0.99-2.19) and 2.73 (1.43-5.22) for cerebral infarction, respectively, compared with the fasting NGT group. On the basis of the subjects with 2h-PG <140 mg/dL group, the adjusted HRs (95% CIs) of subjects with 2h-PG ≥200 mg/dL were 1.71 (1.07-2.72) for stroke and 2.06 (1.20-3.54) for cerebral infarction. Compared to the NGT group, the adjusted HRs (95% CIs) of the subjects with IFG, IGT, and DM were 1.59 (1.10-2.30), 1.34 (0.89-2.00), and 1.86 (1.16-3.00) for stroke and 1.82 (1.13-2.90), 1.55 (0.93-2.56), and 2.43 (1.39-4.26) for cerebral infarction, respectively. Compared to the subjects with HOMA-IR <1.5, the adjusted HRs (95% CIs) of CVD and stroke with HOMA-IR ≥2.5 were 1.45 (1.07-1.96) and 1.61 (1.07-2.42), respectively. Compared to the NGT group without insulin resistance, the IFG and DM groups with insulin resistance were observed the increased risks of stroke (HRs [95% CIs]; 2.05 [1.17-3.57] and 2.11 [1.17-3.83]) and cerebral infarction (HRs [95% CIs]; 2.45 [1.20-5.00] and 3.56 [1.84-6.88]), respectively. Conclusions: Fasting glucose intolerance and insulin resistance are predictive factors for the incidence of stroke and cerebral infarction. Insulin resistance increased the risks of incident stroke and cerebral infarction in general inhabitants with IFG and DM.

scholarly journals GABA administration improves liver function and insulin resistance in offspring of type 2 diabetic rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Azadehalsadat Hosseini Dastgerdi ◽  
Mohammadreza Sharifi ◽  
Nepton Soltani
Keyword(s):  
Insulin Resistance ◽  
Lipid Profile ◽  
Liver Lipid ◽  
Liver Glycogen ◽  
Tolerance Test ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Insulin Tolerance ◽  
Liver Insulin Resistance

AbstractThis study investigated the role of GABA in attenuating liver insulin resistance (IR) in type 2 diabetes parents and reducing its risk in their descendants’ liver. Both sexes’ rats were divided into four groups of non-diabetic control, diabetic control (DC), GABA-treated (GABA), and insulin-treated (Ins). The study duration lasted for six months and the young animals followed for four months. Consequently, hyperinsulinemic-euglycemic clamp was performed for all animals. Apart from insulin tolerance test (ITT), serum and liver lipid profile were measured in all groups. Glycogen levels, expression of Foxo1, Irs2, Akt2, and Pepck genes in the liver were assessed for all groups. Overall, GABA improved ITT, increased liver glycogen levels and decreased lipid profile, blood glucose level, and HbA1c in parents and their offspring in compared to the DC group. GIR also increased in both parents and their offspring by GABA. Moreover, the expression of Foxo1, Irs2, Akt2, and Pepck genes improved in GABA-treated parents and their descendants in compared to DC group. Results indicated that GABA reduced liver IR in both parents and their offspring via affecting their liver insulin signaling and gluconeogenesis pathways.

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