The effects of myo-inositol and probiotic supplementation in a high-fat-fed preclinical model of glucose intolerance in pregnancy

2019 ◽  
Vol 123 (5) ◽  
pp. 516-528 ◽  
Author(s):  
J. F. Plows ◽  
J. M. Ramos Nieves ◽  
F. Budin ◽  
K. Mace ◽  
C. M. Reynolds ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Lactobacillus Rhamnosus ◽  
Tissue Expression ◽  
Tolerance Test ◽  
Preclinical Model ◽  
Oral Glucose ◽  
High Fat ◽  
The Impact

AbstractGlucose intolerance during pregnancy – a major driver of gestational diabetes mellitus (GDM) – has significant short- and long-term health consequences for both the mother and child. As GDM prevalence continues to escalate, there is growing need for preventative strategies. There is limited but suggestive evidence that myo-inositol (MI) and probiotics (PB) could improve glucose tolerance during pregnancy. The present study tested the hypothesis that MI and/or PB supplementation would reduce the risk of glucose intolerance during pregnancy. Female C57BL/6 mice were randomised to receive either no treatment, MI, PB (Lactobacillus rhamnosus and Bifidobacterium lactis) or both (MIPB) for 5 weeks. They were then provided with a high-fat diet for 1 week before mating commenced and throughout mating/gestation, while remaining on their respective treatments. An oral glucose tolerance test occurred at gestational day (GD) 16·5 and tissue collection at GD 18·5. Neither MI nor PB, separately or combined, improved glucose tolerance. However, MI and PB both independently increased adipose tissue expression of Ir, Irs1, Akt2 and Pck1, and PB also increased Pparγ. MI was associated with reduced gestational weight gain, whilst PB was associated with increased maternal fasting glucose, total cholesterol and pancreas weight. These results suggest that MI and PB may improve insulin intracellular signalling in adipose tissue but this did not translate to meaningful differences in glucose tolerance. The absence of fasting hyperglycaemia or insulin resistance suggests this is a very mild model of GDM, which may have affected our ability to assess the impact of these nutrients.

scholarly journals Resolution of glucose intolerance in long-term high-fat, high-sucrose-fed mice

2017 ◽  
Vol 233 (3) ◽  
pp. 269-279 ◽  
Author(s):  
Greg M Kowalski ◽  
Michael J Kraakman ◽  
Shaun A Mason ◽  
Andrew J Murphy ◽  
Clinton R Bruce
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Subcutaneous Adipose Tissue ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
High Fat ◽  
Subcutaneous Adipose ◽  
High Sucrose

The high-fat, high-sucrose diet (HFSD)–fed C57Bl/6 mouse is a widely used model of prediabetes. However, studies typically implement a relatively short dietary intervention lasting between 4 and 16 weeks; as a result, little is known about how a long-term HFSD influences the metabolic profile of these mice. Therefore, the aim of this investigation was to examine the effects of consuming a HFSD for 42 weeks on the development of hyperinsulinaemia and glucose intolerance in male C57Bl/6 mice. Two cohorts of HFSD mice were studied at independent institutes and they underwent an oral glucose tolerance test (OGTT) with measures of plasma insulin and free fatty acids (FFA). Age-matched chow-fed control mice were also studied. The HFSD-fed mice were hyperinsulinaemic and grossly obese, being over 25 g heavier than chow-fed mice, which was due to a marked expansion of subcutaneous adipose tissue. This was associated with a 3-fold increase in liver lipid content. Glucose tolerance, however, was either the same or better than control mice due to the preservation of glucose disposal as revealed by a dynamic stable isotope-labelled OGTT. In addition, plasma FFAs were suppressed to lower levels in HFSD mice during the OGTT. In conclusion, we have made the paradoxical observation that long-term HFSD feeding results in the resolution of glucose intolerance in the C57Bl/6 mouse. Mechanistically, we propose that the gross expansion of subcutaneous adipose tissue increases the glucose disposal capacity of the HFSD-fed mouse, which overcomes the prevailing insulin resistance to improve glucose tolerance.

scholarly journals Distinct Effects of a High Fat Diet on Bone in Skeletally Mature and Developing Male C57BL/6J Mice

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1666
Author(s):  
Dean S. Ross ◽  
Tzu-Hsuan Yeh ◽  
Shalinie King ◽  
Julia Mathers ◽  
Mark S. Rybchyn ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Bone Formation ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Age Groups ◽  
Oral Glucose ◽  
Rna Expression ◽  
High Fat ◽  
Mineral Density ◽  
Skeletal Fragility

Increased risks of skeletal fractures are common in patients with impaired glucose handling and type 2 diabetes mellitus (T2DM). The pathogenesis of skeletal fragility in these patients remains ill-defined as patients present with normal to high bone mineral density. With increasing cases of glucose intolerance and T2DM it is imperative that we develop an accurate rodent model for further investigation. We hypothesized that a high fat diet (60%) administered to developing male C57BL/6J mice that had not reached skeletal maturity would over represent bone microarchitectural implications, and that skeletally mature mice would better represent adult-onset glucose intolerance and the pre-diabetes phenotype. Two groups of developing (8 week) and mature (12 week) male C57BL/6J mice were placed onto either a normal chow (NC) or high fat diet (HFD) for 10 weeks. Oral glucose tolerance tests were performed throughout the study period. Long bones were excised and analysed for ex vivo biomechanical testing, micro-computed tomography, 2D histomorphometry and gene/protein expression analyses. The HFD increased fasting blood glucose and significantly reduced glucose tolerance in both age groups by week 7 of the diets. The HFD reduced biomechanical strength, both cortical and trabecular indices in the developing mice, but only affected cortical outcomes in the mature mice. Similar results were reflected in the 2D histomorphometry. Tibial gene expression revealed decreased bone formation in the HFD mice of both age groups, i.e., decreased osteocalcin expression and increased sclerostin RNA expression. In the mature mice only, while the HFD led to a non-significant reduction in runt-related transcription factor 2 (Runx2) RNA expression, this decrease became significant at the protein level in the femora. Our mature HFD mouse model more accurately represents late-onset impaired glucose tolerance/pre-T2DM cases in humans and can be used to uncover potential insights into reduced bone formation as a mechanism of skeletal fragility in these patients.

scholarly journals Glucose area under the curve during oral glucose tolerance test as an index of glucose intolerance

2015 ◽  
Vol 7 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Kazuhiko Sakaguchi ◽  
Kazuo Takeda ◽  
Mitsuo Maeda ◽  
Wataru Ogawa ◽  
Toshiyuki Sato ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Intolerance ◽  
Glucose Tolerance Test ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance

scholarly journals FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans

2017 ◽  
Vol 102 (10) ◽  
pp. 3806-3813 ◽  
Author(s):  
Ricardo J Samms ◽  
Jo E Lewis ◽  
Luke Norton ◽  
Francis B Stephens ◽  
Christopher J Gaffney ◽  
...  
Keyword(s):  
Dietary Intervention ◽  
Insulin Response ◽  
Tolerance Test ◽  
Fibroblast Growth Factor 21 ◽  
Oral Glucose ◽  
High Fat ◽  
Postprandial Period ◽  
Carbohydrate Consumption ◽  
Adult Humans ◽  
The Impact

Abstract Context Fibroblast growth factor 21 (FGF21) secretion has been shown to respond directly to carbohydrate consumption, with glucose, fructose, and sucrose all reported to increase plasma levels of FGF21 in rodents and humans. However, carbohydrate consumption also results in secretion of insulin. Objective The aim of this study was to examine the combined and independent effects of hyperglycemia and hyperinsulinemia on total and bioactive FGF21 in the postprandial period in humans, and determine whether this effect is attenuated in conditions of altered insulin secretion and action. Methods Circulating glucose, insulin, total and bioactive FGF21, and fibroblast activation protein were measured in adults with and without type 2 diabetes (T2D) following an oral glucose tolerance test (OGTT), and under a series of insulin and glucose clamp conditions and following high-fat diet in healthy adults. Results Circulating total and bioactive FGF21 levels responded acutely to OGTT, and their ratio was attenuated in T2D patients with reduced postprandial insulin response. The clamp studies revealed that insulin but not glucose accounts for the postprandial rise in FGF21. Finally, there was an attenuated rise in FGF21 in response to a high-fat dietary intervention that is known to alter insulin-stimulated substrate utilization in metabolically active tissues. Conclusions Insulin rather than glucose per se increases total and bioactive FGF21 in the postprandial period in adult humans. Understanding the impact of T2D on bioactive FGF21 will have a significant effect upon the efficacy of therapeutic agents designed to target the FGF21 pathway.

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 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.

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