scholarly journals Glucose homeostasis and insulin sensitivity in growth hormone-transgenic mice: a cross-sectional analysis

2010 ◽  
Vol 391 (10) ◽  
Author(s):  
Ravneet K. Boparai ◽  
Oge Arum ◽  
Romesh Khardori ◽  
Andrzej Bartke

Abstract In contrast to its stimulatory effects on musculature, bone, and organ development, and its lipolytic effects, growth hormone (GH) opposes insulin effects on glucose metabolism. Chronic GH overexposure is thought to result in insulin insensitivity and decreased blood glucose homeostatic control. Yet, despite the importance of this concept for basic biology, as well as human conditions of GH excess or deficiency, no systematic assessment of the impact of GH over- expression on glucose homeostasis and insulin sensitivity has been conducted. We report that male and female adult GH transgenic mice have enhanced glucose tolerance compared to littermate controls and this effect is not dependent on age or on the particular heterologous GH transgene used. Furthermore, increased glucose-stimulated insulin secretion, augmented insulin sensitivity, and muted gluconeogenesis were also observed in bovine GH overexpressing mice. These results show that markedly increased systemic GH concentration in GH-transgenic mice exerts unexpected beneficial effects on glucose homeostasis, presumably via a compensatory increase in insulin release. The counterintuitive nature of these results challenges previously held presumptions of the physiology of these mice and other states of GH overexpression or suppression. In addition, they pose intriguing queries about the relationships between GH, endocrine control of metabolism, and aging.

Author(s):  
Silvana Duran-Ortiz ◽  
Kathryn L. Corbin ◽  
Ishrat Jahan ◽  
Nicholas B. Whitticar ◽  
Sarah E Morris ◽  
...  

In the endocrine pancreas, growth hormone (GH) is known to promote pancreatic islet growth and insulin secretion. In this study, we show that GH receptor (GHR) loss in the germline and in adulthood impacts islet mass in general but more profoundly in male mice. GHR knockout (GHRKO) mice have enhanced insulin sensitivity and low circulating insulin. We show that the total cross-sectional area of isolated islets (estimated islet mass) was reduced by 72% in male but by only 29% in female GHRKO mice compared to wild type controls. Also, islets from GHRKO mice secreted ~50% less glucose-stimulated insulin compared to size-matched islets from wild type mice. We next used mice with a floxed Ghr gene to knock down the GHR in adult mice at six-months of age (6mGHRKO) and examined the impact on glucose and islet metabolism. By 12-months of age, female 6mGHRKO mice had increased body fat and reduced islet mass but had no change in glucose tolerance or insulin sensitivity. However, male 6mGHRKO mice had nearly twice as much body fat, substantially reduced islet mass, and enhanced insulin sensitivity, but no change in glucose tolerance. Despite large losses in islet mass, glucose-stimulated insulin secretion from isolated islets was not significantly different between male 6mGHRKO and controls while isolated islets from female 6mGHRKO mice showed increased glucose-stimulated insulin release. Our findings demonstrate the importance of GH to islet mass throughout life and that unique sex-specific adaptations to the loss of GH signaling allow mice to maintain normal glucose metabolism.


Gerontology ◽  
2015 ◽  
Vol 62 (2) ◽  
pp. 163-172 ◽  
Author(s):  
Ross Comisford ◽  
Ellen R. Lubbers ◽  
Lara A. Householder ◽  
Ozan Suer ◽  
Tamara Tchkonia ◽  
...  

Background: Growth hormone (GH)-resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests that long-lived GH-resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. Objective: The objective of this study was to examine WAT senescence, WAT distribution and glucose homeostasis in dwarf GH receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. Methods: 18-month-old female GHA mice and wild-type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose as well as glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase staining to quantify the senescent cell burden, and real-time qPCR to quantify gene expression of senescence markers p16 and IL-6. Results: GHA mice had a 22% reduction in total body weight, a 33% reduction in lean mass and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p < 0.05) and a 1.7-fold increase in extra-/intraperitoneal WAT ratio compared to controls (p < 0.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. Conclusions: Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin sensitivity, but no change in cellular senescence. The similar abundance of WAT senescent cells in GHA and control mice suggests that any protection against generation of senescent cells afforded by decreased GH action, low insulin-like growth factor 1 and/or improved insulin sensitivity in the GHA mice may be offset by their severe adiposity, since obesity is known to increase senescence.


Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 714
Author(s):  
Luciana Baroni ◽  
Anna Rita Sarni ◽  
Cristina Zuliani

Oxidative stress can compromise central nervous system integrity, thereby affecting cognitive ability. Consumption of plant foods rich in antioxidants could thereby protect cognition. We systematically reviewed the literature exploring the effects of antioxidant-rich plant foods on cognition. Thirty-one studies were included: 21 intervention, 4 cross-sectional (one with a cohort in prospective observation as well), and 6 prospective studies. Subjects belonged to various age classes (young, adult, and elderly). Some subjects examined were healthy, some had mild cognitive impairment (MCI), and some others were demented. Despite the different plant foods and the cognitive assessments used, the results can be summarized as follows: 7 studies reported a significant improvement in all cognitive domains examined; 19 found significant improvements only in some cognitive areas, or only for some food subsets; and 5 showed no significant improvement or no effectiveness. The impact of dietary plant antioxidants on cognition appears promising: most of the examined studies showed associations with significant beneficial effects on cognitive functions—in some cases global or only in some specific domains. There was typically an acute, preventive, or therapeutic effect in young, adult, and elderly people, whether they were healthy, demented, or affected by MCI. Their effects, however, are not attributable only to anti-oxidation.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Helen M. Conaglen ◽  
Dennis de Jong ◽  
Veronica Crawford ◽  
Marianne S. Elston ◽  
John V. Conaglen

Purpose. Excess growth hormone secretion in adults results in acromegaly, a condition in which multiple physical changes occur including bony and soft tissue overgrowth. Over time these changes can markedly alter a person’s appearance. The aim of this study was to compare body image disturbance in patients with acromegaly to those with nonfunctioning pituitary adenomas (NFAs) and controls and assess the impact of obesity in these groups.Methods. A cross-sectional survey including quality of life, body image disturbance, anxiety and depression measures, growth hormone, and BMI measurement was carried out.Results. The groups did not differ with respect to body image disturbance. However separate analysis of obese participants demonstrated relationships between mood scales, body image disturbance, and pain issues, particularly for acromegaly patients.Conclusions. While the primary hypothesis that acromegaly might be associated with body image disturbance was not borne out, we have shown that obesity together with acromegaly and NFA can be associated with body image issues, suggesting that BMI rather than primary diagnosis might better indicate whether patients might experience body image disturbance problems.


2015 ◽  
Vol 113 (3) ◽  
pp. 383-402 ◽  
Author(s):  
Trudy Voortman ◽  
Anna Vitezova ◽  
Wichor M. Bramer ◽  
Charlotte L. Ars ◽  
Paula K. Bautista ◽  
...  

High protein intake in early childhood is associated with obesity, suggesting possible adverse effects on other cardiometabolic outcomes. However, studies in adults have suggested beneficial effects of protein intake on blood pressure (BP) and lipid profile. Whether dietary protein intake is associated with cardiovascular and metabolic health in children is unclear. Therefore, we aimed to systematically review the evidence on the associations of protein intake with BP, insulin sensitivity and blood lipids in children. We searched the databases Medline, Embase, Cochrane Central and PubMed for interventional and observational studies in healthy children up to the age of 18 years, in which associations of total, animal and/or vegetable protein intake with one or more of the following outcomes were reported: BP; measures of insulin sensitivity; cholesterol levels; or TAG levels. In the search, we identified 6636 abstracts, of which fifty-six studies met all selection criteria. In general, the quality of the included studies was low. Most studies were cross-sectional, and many did not control for potential confounders. No overall associations were observed between protein intake and insulin sensitivity or blood lipids. A few studies suggested an inverse association between dietary protein intake and BP, but evidence was inconclusive. Only four studies examined the effects of vegetable or animal protein intake, but with inconsistent results. In conclusion, the literature, to date provides insufficient evidence for effects of protein intake on BP, insulin sensitivity or blood lipids in children. Future studies could be improved by adequately adjusting for key confounders such as energy intake and obesity.


2013 ◽  
Vol 304 (5) ◽  
pp. E466-E477 ◽  
Author(s):  
Jianping Ye ◽  
Owen P. McGuinness

Chronic inflammation is a characteristic of obesity and is associated with accompanying insulin resistance, a hallmark of type 2 diabetes mellitus (T2DM). Although proinflammatory cytokines are known for their detrimental effects on adipose tissue function and insulin sensitivity, their beneficial effects in the regulation of metabolism have not drawn sufficient attention. In obesity, inflammation is initiated by a local hypoxia to augment angiogenesis and improve adipose tissue blood supply. A growing body of evidence suggests that macrophages and proinflammatory cytokines are essential for adipose remodeling and adipocyte differentiation. Phenotypes of multiple lines of transgenic mice consistently suggest that proinflammatory cytokines increase energy expenditure and act to prevent obesity. Removal of proinflammatory cytokines by gene knockout decreases energy expenditure and induces adult-onset obesity. In contrast, elevation of proinflammatory cytokines augments energy expenditure and decreases the risk for obesity. Anti-inflammatory therapies have been tested in more than a dozen clinical trials to improve insulin sensitivity and glucose homeostasis in patients with T2DM, and the results are not encouraging. One possible explanation is that anti-inflammatory therapies also attenuate the beneficial effects of inflammation in stimulating energy expenditure, which may have limited the efficacy of the treatment by promoting energy accumulation. Thus, the positive effects of proinflammatory events should be considered in evaluating the impact of inflammation in obesity and type 2 diabetes.


2021 ◽  
Vol 8 (3) ◽  
pp. 112-119
Author(s):  
Ibrahim et al. ◽  

Clopidogrel is widely used for patients with acute coronary syndrome. It is a pro-drug that requires bioactivation by several cytochrome P450 (CYP) enzymes, mainly CYP3A4, CYP2C9, and CYP2C19 enzymes. Lipophilic statins such as atorvastatin are used concomitantly with clopidogrel due to their beneficial effects on morbidity and mortality in the arena of cardiovascular diseases. However, lipophilic statins are eliminated by CYP3A4 and undergo the same metabolic pathway of clopidogrel. Hence, statins may compete with clopidogrel for CYP3A4 enzyme resulting in diminishing the anti-platelet effect of clopidogrel. We aimed to study the impact of concomitant statin therapy on clopidogrel efficacy in patients undergoing percutaneous coronary intervention (PCI) evaluate the clinical relevance of potential clopidogrel and statins interaction and association between use of statins and risk of future adverse cardiac events. A cross-sectional retrospective cohort study was conducted on 50 patients attending Prince Sultan Cardiac Center for follow-up after PCI. All patients discharged on clopidogrel, aspirin, and atorvastatin were later divided into two groups according to the occurrence of MACEs. Statistical analysis was performed by Statistical Package for the Social Science (SPSS; V. 21.0). This study was on adult and geriatric males (72%)and female (28%). More than half of them exhibited major adverse cardiac events (MACEs), of which 48% exhibited it after 4 to 6 months from PCI indexing followed by 1 to 3 months (34%), and the least after 7 to 9 months. A significant association arises between gender and MACEs (P=0.042). Moreover, the average age was significantly higher in patients who experience MACEs compared to others (62.7 vs. 55.4, P=0.037). Regarding comorbidities, hypertension increased in patients with MACEs (73.1%) compared to those without MACEs (45.8%). The average duration of taking clopidogrel was significantly shorter in patients with MACEs compared to those who did not (3.42 vs. 5.54 months, P<0.001). According to the findings of this study, atorvastatin affects clopidogrel efficacy in patients undergoing PCI.


2021 ◽  
Author(s):  
Jinyue Yu ◽  
Mingyue Gao ◽  
Zhuang Wei ◽  
Jonathan CK Wells ◽  
Mary Fewtrell

Abstract Background The COVID-2019 pandemic has placed extensive pressure on health systems and posed a severe public health challenge worldwide. Lockdown measures implemented in many countries have delayed virus spread. However, a considerable number of people have faced unprecedented pressure, especially the pregnant and breast-feeding women, because face-to‐face professional support has been reduced during the lockdown in many countries. Objectives To compare the delivery and infant feeding experiences of women who delivered before (BL) versus during (DL) the Covid-19 pandemic in Beijing, China. Methods Women aged ≥ 18 years with an infant ≤ 18 months of age completed an anonymous survey. Information/links were shared online and via local clinics in Beijing. Logistic regression was performed to assess predictors of breastfeeding during the first 6-months. Results 2233 women provided data; BL 1241 (55.6%), DL 992 (44.4%). The 6-month mostly breastfeeding (MBF, mainly breastfeeding with few non-formula fluids added) rate was significantly higher in the DL mothers (71.6%), compared to the BL mothers (60.6%). MBF was predicted by delivery during the lockdown period (OR1.42, 95% confidence interval 1.06, 1.90), younger maternal age, discussing infant feeding in a feeding support group, and getting support from friends or relatives. Moreover, relative to those little affected by COVID, those who were much affected were less likely to MBF. Conclusion The COVID-19 pandemic and lockdown measures influenced mothers’ planned birth location and breastfeeding intention. However, breastfeeding practice was maintained during the pandemic. The reported breastfeeding rates were high and our results highlight the importance of feeding support as well as potential beneficial effects of increased mother-infant contact during the lockdown period which is relevant even under normal circumstances.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jasmine Paquin ◽  
Jean-Christophe Lagacé ◽  
Martin Brochu ◽  
Isabelle J. Dionne

Skeletal muscle (SM) tissue has been repetitively shown to play a major role in whole-body glucose homeostasis and overall metabolic health. Hence, SM hypertrophy through resistance training (RT) has been suggested to be favorable to glucose homeostasis in different populations, from young healthy to type 2 diabetic (T2D) individuals. While RT has been shown to contribute to improved metabolic health, including insulin sensitivity surrogates, in multiple studies, a universal understanding of a mechanistic explanation is currently lacking. Furthermore, exercised-improved glucose homeostasis and quantitative changes of SM mass have been hypothesized to be concurrent but not necessarily causally associated. With a straightforward focus on exercise interventions, this narrative review aims to highlight the current level of evidence of the impact of SM hypertrophy on glucose homeostasis, as well various mechanisms that are likely to explain those effects. These mechanistic insights could provide a strengthened rationale for future research assessing alternative RT strategies to the current classical modalities, such as low-load, high repetition RT or high-volume circuit-style RT, in metabolically impaired populations.


Sign in / Sign up

Export Citation Format

Share Document