Improvement in Glycemic Control in Mice of Different Age Groups

Author(s):  
Suhadinie Gamage ◽  
Swetha Peddibhotla ◽  
P. Hemachandra Reddy ◽  
Nikhil V. Dhurandhar ◽  
Vijay Hegde

Abstract Aims and Methods The declining ability to control blood glucose with advancement of age is an important health risk factor and may lead to insulin resistance, type-2-diabetes and Alzheimer’s disease. Adenovirus 36(Ad36) improves glycemic control independent of insulin signaling(insulin sparing effect) as evidenced by cell, animal and observational human studies. This property of Ad36 may be useful in correcting aging-related glucose intolerance and related health conditions. Therefore, we determined the effect of Ad36 on glycemic control in older mice, to identify the age group that best responds to Ad36. Six, 12 or 20-month old C57Bl/6 mice on chow diet were each divided into weight-matched groups(mock-infected or Ad36-infected). Body weight was recorded weekly post infection (p.i.) and fasting glucose measured(week 0, 4, 8 and 20 p.i.). Blood glucose and serum insulin were measured during glucose tolerance test(week 0 and 16 p.i.). At week 20 p.i., animals were sacrificed, blood and tissues collected. Results Mice from all age groups showed improvement in glucose clearance post Ad36 infection, but a more profound effect was observed in 6-month old mice compared with mock-infected mice. Under fed conditions though there was no difference in blood glucose at 20 wk p.i., interestingly, Ad36 reduced serum insulin in age groups old mice, compared with control mice. Conclusions These findings suggest Ad36 infected animals improve glycemic control and clear post-prandial gluco00000se increase without increasing insulin secretion in an insulin sparing manner. These beneficial effects provide strong evidence for developing Ad36-based approaches as a novel tool to attenuate age associated glucose intolerance.

2021 ◽  
Vol 9 (1) ◽  
pp. e001981
Author(s):  
Micha Rapoport ◽  
Angela Chetrit ◽  
Dror Cantrell ◽  
Ilya Novikov ◽  
Jesse Roth ◽  
...  

IntroductionWe examined years of potential life lost (YPLL) associated with pre-diabetes as compared with either normoglycemia or diabetes, using data of the Israel cohort of Glucose intolerance, Obesity and Hypertension 40-year follow-up.Research design and methodsMen and women (N=2844, mean age 52.0±8.2 years) who underwent oral glucose tolerance test and anthropometric measurements, during 1976–1982, were followed for mortality until May 2019. Multiple imputation procedures for missing mortality dates and multivariable regression mixed models were applied.ResultsAt baseline, 35.8%, 48.8% and 15.4% individuals were found with normoglycemia, pre-diabetes, and diabetes, respectively. The average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 4.3 years (95% CI 3.3 to 5.2; p<0.001). YPLL were 1 year higher in women with pre-diabetes than in men with pre-diabetes. These differences persisted mainly in individuals younger than 60 years, and those with body mass index (BMI) <25 kg/m2, at baseline. Adjusting for age, sex, country of origin, smoking status, BMI, and blood pressure, the average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 2.0 years (95% CI 1.2 to 2.8; p<0.001). Significant reductions of 5.9 years (95% CI 4.8 to 7.0) on average were observed for diabetes as compared with pre-diabetes and 7.9 years (95% CI 6.7 to 9.1) as compared with individuals with normoglycemia.ConclusionsThis study reveals that life expectancy of middle-aged individuals with pre-diabetes is shorter than of normoglycemic ones. These findings are especially relevant in view of the rising worldwide prevalence of pre-diabetes within younger age groups and underscore the crucial importance of interventions by either lifestyle modification or drug therapy capable of delaying progression from pre-diabetes to diabetes to reduce the YPLL in this high-risk group.


1995 ◽  
Vol 88 (3) ◽  
pp. 301-306 ◽  
Author(s):  
Lorraine A. Nolte ◽  
Samy M. Abdel-Halim ◽  
Iva K. Martin ◽  
Amel Guenifi ◽  
Juleen R. Zierath ◽  
...  

1. The effect of glucose intolerance on insulin-stimulated glucose transport in isolated skeletal muscles was investigated in male F, hybrids of spontaneously diabetic GK (Goto—Kakizaki) and control Wistar rats at 1 and 2 months of age. 2. Hybrid rats are characterized by markedly impaired glucose-induced insulin secretion. The area under the blood glucose curve was significantly higher following an intraperitoneal glucose injection (2 g/kg) in hybrid rats in both age groups than in the control rats (P < 0.001). In 2-month-old hybrid rats the incremental area under the insulin curve during the intraperitoneal glucose tolerance test was not different from that of control rats. Serum cholesterol, triacylglycerol or plasma free fatty acid levels did not differ between the groups. Fasting and post-prandial plasma glucose concentrations were elevated in 2-month-old hybrid rats compared with control rats (54%, P < 0.05, and 27%, P < 0.05, respectively), but were not differerent in 1-month-old rats. Plasma insulin did not differ between the hybrid and control rats in the fasting or post-prandial state at either age studied. 3. The insulin dose—response curves for 3-O-methylglucose transport did not differ between 1-month-old hybrid and control rats for either the soleus or epitrochlearis muscle. The insulin dose—response curve for the epitrochlearis, but not for the soleus, muscle from 2-month-old hybrid rats was shifted to the right compared with the curve from the control animals (P < 0.05). 4. In conclusion, the hybrid rat is a non-obese, non-hyperinsulinaemic animal model, which at a young age is characterized by impaired insulin secretion and moderate glucose intolerance. In this glucose-intolerant rat model, mild peripheral insulin resistance gradually develops, as reflected by the decreased insulin-induced glucose transport in the fast-twitch epitrochlearis muscle. It is suggested that the elevated blood glucose per se may have contributed to the slight decrease in peripheral insulin action.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Li Ang ◽  
Liu Yuguang ◽  
Wang Liying ◽  
Zhang Shuying ◽  
Xu Liting ◽  
...  

Ergosterol (ERG) has been widely used in the development of novel drugs due to its unique physiological function. However, little is known about the protective effects of ERG on diabetes. Hence, the current study was designed to evaluate the positive role of ergosterol on streptozotocin- (STZ-) induced diabetes in mice. Oral glucose tolerance test (OGTT) was carried out to assess blood glucose level. Biochemical parameters such as uric acid, creatinine, serum insulin, triglycerides (TG), and total cholesterol (TC) were also measured. Pathological condition of kidney was examined by hematoxylin-eosin (H&E) staining. The expressions of PI3K, p-PI3K, Akt, p-Akt, NF-κBp65, p-NF-κBp65, IκBα, and p-IκBαwere analyzed by western blot. ERG significantly reduced the concentrations of blood glucose, uric acid, creatinine, TG, and TC. Serum insulin was elevated with ERG treatment. In addition, renal pathologic changes of diabetes mice were also alleviated by ERG. Obtained data revealed that ERG restored the levels of PI3K/Akt/NF-κB signaling-related proteins in comparison with diabetes mice. Above all, it could be assumed that ERG might play a positive role in regulating STZ-induced diabetes through suppressing PI3K/Akt/NF-κB pathway.


1980 ◽  
Vol 93 (2) ◽  
pp. 179-185 ◽  
Author(s):  
Ove R. Nilsson ◽  
Bertil Kågedal ◽  
Lennart Tegler

Abstract. The insulin release and the glucose disappearance rate (K-value) during an iv glucose tolerance test were evaluated in 20 hyperthyroid patients before and during treatment with either a non-selective (propranolol, n = 10) or a selective (metoprolol, n = 10) β-l-adrenoceptor blocking agent. Mean daily doses were 240 mg of propranolol and 280 mg of metoprolol, administered four times daily for 10 to 14 days. The insulin increase after glucose injection remained unchanged during treatment with each drug. Fasting blood glucose concentrations and the K-values were not altered during treatment. Sixteen patients were re-investigated 10 to 36 weeks later when euthyroid due to treatment by surgery, thyrostatic drugs or radioiodine. In the euthyroid state mean serum insulin concentrations after the glucose load were not significantly different from the values found when the patients were hyperthyroid. However, mean fasting blood glucose concentrations decreased from 5.5 mmol/l to 5.0 (P < 0.01) and the mean K-value increased from 1.5 to 2.0 (P < 0.05) when the patients were euthyroid. It is concluded that short-term treatment of hyperthyroid patients with non-selective or selective β-l-adrenoceptor blocking agents does not impair the glucose stimulated insulin secretion or the carbohydrate tolerance.


2021 ◽  
Vol 59 (3) ◽  
Author(s):  
Irena Crnić ◽  
Tajana Frančić ◽  
Petar Dragičević ◽  
Vedran Balta ◽  
Verica Dragović-Uzelac ◽  
...  

Research background. The use of plants and their extracts in treatments of chronic diseases is widely known in traditional medicine. The aim of this study is to determine the effects of 10-day consumption of Prunus spinosa L. flower extract on blood glucose, glycaemic load, serum α-amlyase and serum insulin, in normoglycaemic and hypergycaemic (alloxan) mice model. Experimental approach. Normoglycemic and hyperglycemic (alloxan treated, 150 mg/kg body mass) C57BL/6 mice were treated daily, during 10 days, with Prunus spinosa L. flower extract by gavage. The sugar content within extract was determined by HPLC analysis. In mice, blood and serum blood glucose level and OGTT-test were determined by blood glucometer. Serum insulin was determined by ELISA assay and α-amlyase by colourimetric assay. Results and conclusions. The Prunus spinosa L. flower extract increased glucose in normoglycaemic mice by 30 % after 1st and 5th day and by 17 % after 10th day of consumption in normoglycaemic mice. It is a consequence of released sugars because sugar analysis revealed 59.8 mg/L monosaccharides, mainly fructose (55.7 mg/L) and glucose (24.3 mg/L) within the extract. On the opposite, the extract consumption, reduced serum blood glucose in alloxan-induced hyperglycaemic mice by 29 % after 10 days of treatment. Oral glucose tolerance test also confirmed that that in the hyperglycaemic group treated with Prunus spinosa L. flower extract glucose homeostasis was improved and showed decrease in blood glucose, since the blood glucose over the period of 120 min, glucose homeostasis is faster achieved after treatment with shows that in Prunus spinosa L. flower extract. Serum insulin increased by 49 % and serum alpha amylase by 46 % after 10 days of treatment with Prunus spinosa L. flower extract in hyperglycaemic group. Thus, it can be concluded that Prunus spinosa L. flower extract improved glucose tolerance, enhanced insulin secretion and lowered serum α-amylase activity. Novelty and scientific contribution. The results examined for the first time the potential of Prunus spinosa L. flower extract in hyperglycaemia management.


2018 ◽  
Vol 10 (4) ◽  
pp. 502-506 ◽  
Author(s):  
R. Tarevnic ◽  
F. Ornellas ◽  
C. A. Mandarim-de-Lacerda ◽  
M. B. Aguila

AbstractWe aimed to evaluate the impact of maternal exercise training on the offspring metabolism and body size caused by father obesity. C57BL/6 male 4-week-old mice were fed a high-fat diet (HF father) or control diet (C father), while equal age female mice were fed only a C diet and were separated into two groups: trained (T mother) and non-trained (NT mother), and at 12 weeks of age mice were mated. A continuous swimming protocol was applied for 10 weeks (before and during gestation), and offspring were followed since weaning until sacrifice (at 12 weeks of age). HF father, compared to C father, showed obesity, elevated total cholesterol (TC) and triglycerides (TG), and glucose intolerance. Both sexes HF/NT offspring showed hyperglycemia, glucose intolerance and high levels of TC and TG, without obesity. However, HF/T offspring showed data close to C/NT, demonstrating the beneficial effect of maternal exercise in the offspring of obese fathers.


2020 ◽  
Vol 2020 ◽  
pp. 1-23
Author(s):  
Xuan Guo ◽  
Wen Sun ◽  
Guangyuan Xu ◽  
Dan Hou ◽  
Zhuo Zhang ◽  
...  

Diabetes is one of the most serious chronic diseases. Numerous drugs including oral agents and traditional Chinese medicines, such as sitagliptin phosphate (SP) and Fuzhujiangtang granules (FJG), have been discovered to treat diabetes and used in combination in clinical practice. However, the exact effect and underlying mechanism of using combined medicine is not clear. In this study, we compared the antidiabetic effect of SP, FJG, and SP plus FJG (SP-FJG) using forty 8-week-old Zucker diabetic fatty (ZDF) rats and 10 age-matched Zucker lean rats as the normal control group. ZDF rats were treated with different therapies, respectively, for 6 weeks. The study showed that the fast blood glucose, random blood glucose (RBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), homeostasis model of assessment-insulin resistance index, triglyceride (TC), superoxide dismutase, and malondialdehyde of each treatment group were improved when compared with the diabetes mellitus (DM) control group. Using SP-FJG in combination had better improvements in OGTT, fast serum insulin levels, TNF-α, and IL-6 compared with using SP individually. Besides, the increased LDL and TC caused by using SP was attenuated by using FJG in combination. Meanwhile, compared with the DM group, 1781 differentially expressed genes (DEGs) (including 1248 mRNA, 211 ncRNA, 202 cirRNA, and 120 miRNA) were enriched in 58 pathways. Through analysis of ceRNA networks, we found that rno-miR-326-3p, rno-miR-423-5p, rno-miR-15b-5p, rno-let-7c-5p, and rno-let-7b-5p were related to pharmacodynamics in different groups. By analyzing the protein-protein interaction (PPI) and coexpression networks of the transcriptomes of different groups, it is inferred that Lrrk2 and Irak3 may be pharmacodynamic genes for type 2 diabetes mellitus (T2DM). Our research compared the treatment of SP, FJG, and SP-FJG and acquainted the PPI network, coexpression network, mutations, and pharmacodynamics genes, which reveals the new mechanisms of pathogenesis of T2DM.


2019 ◽  
Vol 6 (14) ◽  
pp. 493-496
Author(s):  
Rishan Singh

The function of the human body are controlled by enzymes and hormones. Similarly, in the laboratory, the enzyme, glucose oxidase, is used to hydrolyse glucose. In the human body, glucose and insulin control blood glucose levels, which are dependent on food intake. In this study, the enzyme specificity and glucose concentration of sugar solutions would be estimated. In order to achieve this, an experiment involving the use of indicator strips and a two-fold serial dilution was performed. Furthermore, conclusions on blood glucose and serum insulin levels would also be discussed from a given data set.


1994 ◽  
Vol 39 (3) ◽  
pp. 71-73
Author(s):  
C. Bengtsson ◽  
L. Lapidus

Felodipine,1 a vascular selective antihypertensive calcium antagonist, was compared with hydrochlorothiazide, a diuretic, with respect to glucose tolerance. An open crossover study was performed comprising 16 non-diabetic hypertensive women (age range 59–75 years). The women continued to take a beta-blocker as a basal therapy. Each treatment period lasted three months. The blood pressure was similar irrespective of treatment. Blood glucose values were not significantly different during the oral glucose tolerance test. Serum insulin levels after glucose administration were lower when the patients were treated with felodipine than when taking hydrochlorothiazide. A possible explanation for this observation may be an increased insulin release as a consequence of treatment with a diuretic in order to maintain normal blood glucose levels during the glucose tolerance test. Felodipine appears preferable to hydrochlorothiazide as an addition to a beta blocker in hypertensive patients from a glucose metabolism point of view.


2005 ◽  
Vol 39 (10) ◽  
pp. 1606-1610 ◽  
Author(s):  
J Megan Schoeffler ◽  
Dennis AK Rice ◽  
Douglas G Gresham

BACKGROUND: The medical literature supports the fact that sliding scale dosing of insulin is an ineffective means to control blood glucose concentrations. Despite this, many clinicians still use sliding scale insulin (SSI) regimens. A better tool for controlling hyperglycemia is clearly needed. OBJECTIVE: To compare the efficacy of an algorithm using 70/30 insulin with traditional SSI dosing for glycemic control in hospitalized patients with type 2 diabetes. METHODS: A prospective, cohort, comparative trial was conducted at a 644-bed, 2-hospital, regional referral health system. Patients were screened for enrollment based on orders received in the pharmacy for sliding scale dosing of insulin. Patients were treated either following an algorithm using 70/30 insulin twice daily or traditional SSI dosing as written by the prescribing physician. RESULTS: Twenty patients with type 2 diabetes were involved in this pilot trial: 10 were treated with the 70/30 insulin algorithm and 10 received a physician-determined traditional SSI regimen. Patients treated based on the 70/30 insulin algorithm achieved better glycemic control (p = 0.042). No difference between the groups was detected in the average number of insulin units administered, insulin injections, or days patients spent on their respective insulin regimens. CONCLUSIONS: Glycemic control with the 70/30 insulin algorithm was superior to traditional SSI dosing.


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