scholarly journals Chronic peptide-based GIP receptor inhibition exhibits modest glucose metabolic changes in mice when administered either alone or combined with GLP-1 agonism

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249239
Author(s):  
Jason A. West ◽  
Anastasia Tsakmaki ◽  
Soumitra S. Ghosh ◽  
David G. Parkes ◽  
Rikke V. Grønlund ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Fasting Blood Glucose ◽  
Chronic Administration ◽  
Dual Therapy ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Beneficial Effects ◽  
Gut Hormone ◽  
Gip Receptor

Combinatorial gut hormone therapy is one of the more promising strategies for identifying improved treatments for metabolic disease. Many approaches combine the established benefits of glucagon-like peptide-1 (GLP-1) agonism with one or more additional molecules with the aim of improving metabolic outcomes. Recent attention has been drawn to the glucose-dependent insulinotropic polypeptide (GIP) system due to compelling pre-clinical evidence describing the metabolic benefits of antagonising the GIP receptor (GIPR). We rationalised that benefit might be accrued from combining GIPR antagonism with GLP-1 agonism. Two GIPR peptide antagonists, GIPA-1 (mouse GIP(3–30)NH2) and GIPA-2 (NαAc-K10[γEγE-C16]-Arg18-hGIP(5–42)), were pharmacologically characterised and both exhibited potent antagonist properties. Acute in vivo administration of GIPA-1 during an oral glucose tolerance test (OGTT) had negligible effects on glucose tolerance and insulin in lean mice. In contrast, GIPA-2 impaired glucose tolerance and attenuated circulating insulin levels. A mouse model of diet-induced obesity (DIO) was used to investigate the potential metabolic benefits of chronic dosing of each antagonist, alone or in combination with liraglutide. Chronic administration studies showed expected effects of liraglutide, lowering food intake, body weight, fasting blood glucose and plasma insulin concentrations while improving glucose sensitivity, whereas delivery of either GIPR antagonist alone had negligible effects on these parameters. Interestingly, chronic dual therapy augmented insulin sensitizing effects and lowered plasma triglycerides and free-fatty acids, with more notable effects observed with GIPA-1 compared to GIPA-2. Thus, the co-administration of both a GIPR antagonist with a GLP1 agonist uncovers interesting beneficial effects on measures of insulin sensitivity, circulating lipids and certain adipose stores that seem influenced by the degree or nature of GIP receptor antagonism.

scholarly journals GESTATIONAL DIABETES MELLITUS

2012 ◽  
Vol 19 (04) ◽  
pp. 462-468
Author(s):  
M. IKRAM ◽  
SYED HAIDER HASAN ALAM ◽  
SHAFQAT MUKHTAR ◽  
M. Saeed
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Gestational Diabetes Mellitus ◽  
Glucose Tolerance Test ◽  
Fasting Blood Glucose ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance

Introduction: Gestational diabetes mellitus is common disorder in pregnancy. It is associated with adverse pregnancy outcome. There is no consensus regarding the optimal approach to screening of gestational diabetes mellitus. The present study has tried toobserve the value of fasting blood glucose in screening of gestational diabetes. Objective: To determine the frequency of patients in whomfasting blood glucose and 100gm glucose tolerance show agreement for screening of gestational diabetes mellitus at 24 -28 wks. Studydesign: Comparative cross sectional study. Settings: The study was conducted at Gynecology and Obstetrics department Shaikh ZayedFederal Post Graduate Institute Lahore. Duration of study with dates: 6 months from 12Nov 2010 to 11 May 2011. Material and method: Thestudy included 135 booked patients with positive family history of diabetes mellitus. All patients underwent fasting blood glucose at 24-28 weeksof gestation, regardless of results of fasting blood glucose on next visit they underwent 100g oral glucose tolerance test (OGTT). The agreementbetween fasting blood glucose and 100g oral glucose tolerance test was calculated in frequency and percentages. Results: The mean age ofwomen in studied population was 27.15±3.70.Out of 135 patients 86.7 %( 117) showed agreement between results of fasting blood glucose and100g OGTT while 13.31 %( 18) showed no agreement between both of the tests. Conclusions: Fasting blood glucose is a good screeningoption for gestational diabetes mellitus along with positive history. It provides a simple, cheap and more practical test for screening of gestationaldiabetes mellitus. However diagnostic confirmation with 100g OGTT should be done.

scholarly journals Compound Danshen Dripping Pills Prevented Leptin Deficiency-Induced Hepatic ER Stress, Stimulated Autophagy, and Improved Insulin Resistance of ob/ob Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yanan Shi ◽  
Dan Liu ◽  
Jihong Yuan ◽  
Lihui Yan ◽  
Zhenfeng Zhan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Er Stress ◽  
Heart Diseases ◽  
Fasting Blood Glucose ◽  
Underlying Mechanism ◽  
Hepatic Function ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Signal Sensitivity

Compound Danshen dripping pills (CDDP) is widely used for the treatment of coronary arteriosclerosis and ischemic heart diseases for decades of years. In our study, we interestingly discovered the effects and mechanism of CDDP on insulin resistance that increase the risk factor of cardiovascular diseases. Effects of CDDP on fasting blood glucose, the insulin tolerance test (ITT), the oral glucose tolerance test (OGTT), hepatic function, and underlying mechanism were analyzed in ob/ob mice. CDDP was found improving the impaired insulin signal sensitivity of ob/ob mice by ameliorating insulin and glucose tolerance, improving hepatic phosphorylation of the insulin receptor substrate-1 on Ser 307 (pIRS1) of ob/ob mice, and restoring hepatic function by decreasing serum ALT and AST, which increased in ob/ob mice serum. Decreasing hepatic phosphorylation of pancreatic ER kinase (PERK) and inositol-requiring enzyme-1 (IRE1) regulating hepatic ER stress in the liver of ob/ob mice were increased by CDDP. Furthermore, CDDP was also found stimulating ob/ob mice hepatic autophagy by increasing the expression of Beclin1 and LC3B, while decreasing P62 expression. Our study discovered an important role of CDDP on improving ob/ob mice insulin resistance and liver function probably through relieving hepatic ER stress and stimulating hepatic autophagy, which would broaden the application value and provide more benefits for treating cardiovascular patients. This trial is registered with NCT01659580.

scholarly journals Metabolic phenotype in Darier disease: a cross-sectional clinical study

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Tara Ahanian ◽  
Philip Curman ◽  
Ivone U. S. Leong ◽  
Kerstin Brismar ◽  
Etty Bachar-Wikstrom ◽  
...  
Keyword(s):  
Clinical Study ◽  
Glucose Tolerance ◽  
Er Stress ◽  
Glucose Tolerance Test ◽  
Fasting Blood Glucose ◽  
Tolerance Test ◽  
Metabolic Phenotype ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Cross Sectional

Abstract Background Human data supporting a role for endoplasmic reticulum (ER) stress and calcium dyshomeostasis in diabetes is scarce. Darier disease (DD) is a hereditary skin disease caused by mutations in the ATP2A2 gene encoding the sarcoendoplasmic-reticulum ATPase 2 (SERCA2) calcium pump, which causes calcium dyshomeostasis and ER stress. We hypothesize that DD patients have a diabetes-like metabolic phenotype and the objective of this study was to examine the association between DD with impaired glucose tolerance and diabetes. Methods Cross-sectional clinical study on 25 DD patients and 25 matched controls. Metabolic status was assessed primarily by fasting blood glucose, oral glucose tolerance test, HOMA2-%S (insulin resistence) and HOMA2-%B (beta cell function). Results DD subjects showed normal oral glucose tolerance test and HOMA2-%S, while fasting blood glucose was lower and c-peptide as well as HOMA2-%B was higher. Conclusion Increased HOMA2-%B values are indicative of increased basal insulin secretion which is a type of beta cell dysfunction associated to diabetes development. These results supports a role of ER stress in diabetes pathophysiology and contribute to the understanding of DD as a multi-organ syndrome.

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 Preconception air pollution exposure and glucose tolerance in healthy pregnant women in a middle income country

2020 ◽  
Author(s):  
Mehdi Zareie ◽  
Ali Gohari ◽  
Leyla Haghighi ◽  
Hafez Heydari ◽  
Mohammad miri
Keyword(s):  
Air Pollution ◽  
Glucose Tolerance ◽  
Pregnant Women ◽  
Fasting Blood Glucose ◽  
Tolerance Test ◽  
Middle Income Country ◽  
Income Country ◽  
P Value ◽  
Oral Glucose ◽  
Middle Income

Abstract Background: The effect of preconception exposure to air pollution on glucose tolerance during pregnancy in developing and middle-income countries is under debate yet. Therefore, this study aimed to assess the relationship between exposure to ambient particulate matter (PM) and traffic indicators with glucose tolerance in healthy pregnant women in Sabzevar, Iran (2019). Methods: Accordingly, 250 healthy pregnant women with singleton pregnancies of 24-26 weeks of gestations were participated in our study. Land use regression (LUR) models were applied to estimate the annual mean of PM1, PM2.5 and PM10 at residential address. Traffic indicators, including distance from home to the nearest major road (DHMR) as well as total streets length in 100, 300 and 500m buffers around the home (TSL-100, 300 and 500) were calculated using the street map of Sabzevar. Oral glucose tolerance test (OGTT) was used to assess glucose tolerance during pregnancy. Multiple linear regression adjusted for relevant covariates was used to estimate the association of fasting blood glucose (FBG), 1-h and 2-h post-load glucose with PMs and traffic indicators. Results: Exposure to PM1, PM2.5 and PM10 was significantly associated with higher FBG concentration. Higher TSL-100 was associated with higher FBG and 1-h glucose concentrations. Each one interquartile range (IQR) increase in DHMR the levels of FBG and 1-h post-load glucose were decreased -3.42 mg/dL (95% confidence interval (CI): -4.47, -2.37, P-value < 0.01) and -4.65 mg/dL (95% CI: -8.03, -1.26, P-value < 0.01), respectively. Conclusion: We found higher preconception exposure to air pollution and exposure to air pollution during pregnancy were negatively associated with glucose tolerance during pregnancy in a middle income country.

scholarly journals The Association between Hyperglycemia and Fracture Risk in Middle Age. A Prospective, Population-Based Study of 22,444 Men and 10,902 Women

2008 ◽  
Vol 93 (3) ◽  
pp. 815-822 ◽  
Author(s):  
A. H. Holmberg ◽  
P. M. Nilsson ◽  
J-Å. Nilsson ◽  
K. Åkesson
Keyword(s):  
Blood Glucose ◽  
Glucose Tolerance ◽  
Fracture Risk ◽  
Fasting Blood Glucose ◽  
Osteoporotic Fractures ◽  
Insulin Level ◽  
Tolerance Test ◽  
Glucose Measurement ◽  
Oral Glucose ◽  
Multiple Fractures

Abstract Aims: Type 1 diabetes mellitus is associated with increased fracture risk, whereas the risk associated with type 2 diabetes is less obvious. Elevated fasting blood glucose and high 2-h glucose during an oral glucose tolerance test indicate impaired glucose tolerance or diabetes. The associations among fasting blood glucose, 2-h glucose, and the risk of fracture were investigated. Methods: The Malmö Preventive Project consists of 22,444 men (44 ± 6.6 yr) and 10,902 women (50 ±7.4 yr), with a follow-up of 19 yr (±3.9) and 15 yr (±4.5) for incident fractures. Baseline assessment included multiple examinations and lifestyle information. A logistic regression model was used. Adjustments were made for age, body mass index (BMI), and smoking. Results: Low-energy fractures were recorded in 1246 men and 1236 women. A 2-h glucose measurement between 4.3 and 6.2 mmol/liter in men (second and third quartile), and above 6.5 mmol/liter in women (third and fourth quartile), adjusted for age, BMI, and smoking, was significantly associated with a decreased risk of multiple fractures, in men [odds ratios (ORs) 0.57–0.71] and women (ORs 0.38–0.66). In women, a 2-h glucose measurement above 7.5 mmol/liter was associated with a decreased risk of osteoporotic fractures (OR 0.57, 95% confidence interval 0.44–0.74). Conclusions: In middle-aged men and women, elevated 2-h glucose levels were associated with decreased risks of multiple and osteoporotic fractures, independent of age, BMI, and smoking. A high 2-h glucose level is characterized by peripheral insulin resistance with a high insulin level. Our findings indirectly suggest a positive effect on bone from hyperglycemia.

The Relation Between Glucose Tolerance and Insulin Binding to Circulating Monocytes in Obese Children

PEDIATRICS ◽  
1982 ◽  
Vol 70 (4) ◽  
pp. 633-637
Author(s):  
Kaichi Kida ◽  
Noriyoshi Watanabe ◽  
Yoshiki Fujisawa ◽  
Yoshinori Goto ◽  
Hiroshi Matsuda
Keyword(s):  
Glucose Tolerance ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Tolerance Test ◽  
Quantitative Relation ◽  
Immunoreactive Insulin ◽  
Oral Glucose ◽  
Obese Children

The quantitative relation between insulin binding to circulating monocytes in vitro and glucose tolerance in obese children in vivo is reported. Sixty-one obese children and 11 healthy control children participated in this study. The oral glucose tolerance test (OGTT) was performed by giving them glucose (1.75 gm/kg of body weight), orally in the morning, and the binding of 125I-labeled insulin to circulating monocytes in vitro was measured prior to OGTT. The glucose tolerance expressed by ΣBS (milligrams/100 ml), the sum of the plasma glucose (blood sugar [BS]) values at OGTT, was significantly correlated with the degree of overweight (r = .316, P &lt; .01) and more highly with ΣIRI (microunits per milliliter), the sum of immunoreactive insulin (IRI) values at OGTT (r = .512, P &lt; .001). Insulin binding to monocytes in vitro (picograms/106 cells) was inversely correlated with the degree of overweight (r = -. 687, P &lt; .001). Furthermore, ΣBS was inversely correlated significantly with insulin binding to monocytes in vitro (r = -.435, P &lt; .002). These data suggest that the decrease of insulin receptors might be one cause for the impairment of the glucose tolerance associated with obesity in children.

Risk of metformin failure in the treatment of women with festational diabetes

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Kimberly M. Herrera ◽  
Jennie P. Ou ◽  
Malini D. Persad ◽  
James Bernasko ◽  
Diana Garretto ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Failure Rate ◽  
Glucose Tolerance Test ◽  
Fasting Blood Glucose ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Failure Group

Abstract Objectives To estimate the metformin failure rate in women with gestational diabetes. Methods The study was designed as a retrospective cohort of women diagnosed with gestational diabetes by the 75 g 2 h oral glucose tolerance test. Women were placed into two groups: metformin success (107 patients not requiring insulin therapy) or metformin failure (15 patients requiring the addition of, or, transition to insulin). Primary outcome: rate of metformin failure. Secondary outcomes: maternal and neonatal factors. Results The failure rate of metformin was 15% (19/122 women) in the study. The failure group was more likely to have 3 abnormal values on a 2-h 75 g oral glucose tolerance test (37% (n=7/19) vs. 15% (n=15/103), p=0.02). Patients who failed had higher average fasting blood glucose levels on the glucose tolerance test as well as on pretreatment fasting finger stick values. Those who failed metformin were diagnosed with gestational diabetes and started on metformin earlier in gestation. Conclusions Overall low rate of metformin failure in treatment of gestational diabetes.

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