Adaptation, constraint, and the function of the gluconeogenic pathway

1988 ◽  
Vol 66 (5) ◽  
pp. 1059-1068 ◽  
Author(s):  
Thomas W. Moon
Keyword(s):  
De Novo ◽  
Activity Level ◽  
Adaptive Responses ◽  
Muscle Lactate ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Metabolic Sequence ◽  
Gluconeogenic Enzyme ◽  
Quantitative Changes

Gluconeogenesis is responsible for the de novo synthesis of glucose (and glycogen) from precursors including lactate, amino acids, glycerol, and fructose. This metabolic sequence is highly constrained by design features including enzyme composition and tissue localization, but demonstrates a variety of adaptive patterns which are critical to the maintenance of blood glucose levels optimal for animal function. This review identifies the adaptive responses of gluconeogenesis when glucose levels are challenged by changes in diet (both quality and quantity) and in activity level, and by environmental disturbances. Five adaptive patterns are identified: (i) quantitative changes in gluconeogenic enzyme activities and their subcellular distribution; (ii) alterations in tissue demand for glucose; (iii) existence of in situ skeletal muscle lactate cycling; (iv) quantity and type of gluconeogenic precursors; and (v) regulation of gluconeogenesis. The validity of the omnivorous mammalian model in our understanding of gluconeogenesis is discussed.

scholarly journals Exposure to cholinesterase inhibiting insecticides and blood glucose level in a population of Ugandan smallholder farmers

2020 ◽  
Vol 77 (10) ◽  
pp. 713-720
Author(s):  
Martin Rune Hassan Hansen ◽  
Erik Jørs ◽  
Annelli Sandbæk ◽  
Daniel Sekabojja ◽  
John C Ssempebwa ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Fruits And Vegetables ◽  
Smallholder Farmers ◽  
Fixed Effect ◽  
Phase Changes ◽  
Activity Level ◽  
Reverse Causality ◽  
Mixed Effect ◽  
Glucose Levels ◽  
Blood Glucose Levels

ObjectivesThe risk of diabetes mellitus may be elevated among persons exposed to some pesticides, including cholinesterase-inhibiting insecticides (organophosphates and carbamates). The objective of this study was to investigate how acetylcholinesterase activity was associated with mean blood glucose levels among smallholder farmers in Uganda.MethodsWe conducted a short-term follow-up study among 364 smallholder farmers in Uganda. Participants were examined three times from September 2018 to February 2019. At each visit, we measured glycosylated haemoglobin A (HbA1c) as a measure of long-term average blood glucose levels. Exposure to organophosphate and carbamate insecticides was quantified using erythrocyte acetylcholinesterase normalised by haemoglobin (AChE/Hb). For a subgroup of participants, fasting plasma glucose (FPG) was also available. We analysed HbA1c and FPG versus AChE/Hb in linear mixed and fixed effect models adjusting for age, sex, physical activity level, and consumption of fruits and vegetables, alcohol and tobacco.ResultsContrary to our hypothesis, our mixed effect models showed significant correlation between low AChE/Hb and low HbA1c. Adjusted mean HbA1c was 0.74 (95% CI 0.17 to 1.31) mmol/mol lower for subjects with AChE/Hb=24.3 U/g (35th percentile) compared with subjects with AChE/Hb=25.8 U/g (50th percentile). Similar results were demonstrated for FPG. Fixed effect models showed less clear correlations for between-phase changes in AChE/Hb and HbA1c.ConclusionsOur results do not clearly support a causal link between exposure to cholinesterase-inhibiting insecticides and elevated blood glucose levels (expressed as HbA1c and FPG), but results should be interpreted with caution due to the risk of reverse causality.

Biochemical Effects of Oxygen at High Pressure in Rats

1973 ◽  
Vol 51 (9) ◽  
pp. 673-678 ◽  
Author(s):  
E. W. Banister ◽  
A. J. Davison ◽  
N. M. G. Bhakthan ◽  
C. Asmundson
Keyword(s):  
High Pressure ◽  
Alkaline Phosphatase ◽  
Blood Glucose ◽  
Lactate Dehydrogenase ◽  
Nadh Dehydrogenase ◽  
Krebs Cycle ◽  
Muscle Lactate ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Hyperbaric Conditions

Changes in brain and muscle lactate dehydrogenase, cytochrome oxidase, and NADH dehydrogenase (cytochrome c reductase) have been measured in rats convulsed by exposure to oxygen at high pressure 6 ATA (OHP). Blood glucose levels and some plasma and serum enzymes (lactate dehydrogenase, alkaline phosphatase, aspartate transaminase, and creatine kinase) were measured simultaneously. The lack of widespread inhibition of several markers for the glycolytic sequence, the Krebs cycle, or the cytochrome chain, together with elevated blood glucose levels in hyperoxia and increased blood alkaline phosphatase and lactate dehydrogenase in all hyperbaric conditions (and as well as oxygen), suggests tissue damage and a generalized etiology for the convulsive state.

scholarly journals ALTERATIONS IN FASTING BLOOD GLUCOSE LEVELS IN INDIVIDUALS EXPOSED TO HIGH PROFESSIONAL STRESS

2020 ◽  
pp. 44-47
Author(s):  
Farheen Fatima ◽  
D. Joya Rani ◽  
B. Chandini Rani
Keyword(s):  
Blood Glucose ◽  
Mental Stress ◽  
Acute Stress ◽  
Stress Hormones ◽  
Fasting Blood Glucose ◽  
Adaptive Responses ◽  
Lifestyle Modifications ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Increased Risk

Stress refers to processes involving perception, appraisal and response to noxious events or stimuli. While acute stress can activate adaptive responses, chronic stresses are detrimental to health by altering various physiological parameters1. One such change involves blood glucose levels. This study was done to detect any alterations in blood glucose levels on exposure to chronic mental stress. Mental stress was assessed using the Stress scale of the DASS – 42 questionnaire. Correlation between stress perception and altered blood glucose levels was seen. Reasons for this change range from effects of stress hormones on carbohydrate & lipid metabolism to changes in brain which promote stress eating. There is increased risk for obesity, Diabetes Mellitus and Metabolic syndrome in future. Interventions to reduce this risk include lifestyle modifications which include caloric restriction, increasing physical activity and getting involved in customised activities which reduce stress.

EFFECT OF NUTRITIONAL STATE ON HORMONAL REGULATION OF LIVER ENZYMES

1965 ◽  
Vol 43 (9) ◽  
pp. 1548-1563 ◽  
Author(s):  
G. Weber ◽  
R. L. Singhal ◽  
S. K. Srivastava
Keyword(s):  
Hormonal Regulation ◽  
Liver Enzymes ◽  
Specific Activity ◽  
Amino Acid Level ◽  
Pronounced Increase ◽  
Gluconeogenic Enzymes ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Acute Starvation ◽  
Gluconeogenic Enzyme

The ability of enzyme-forming systems to meet the challenge of starvation and produce vital metabolites for maintaining homeostasis was studied. The preferential maintenance of hepatic gluconeogenic enzymes in starvation can be blocked by hypophysectomy and also by inhibitors of protein synthesis, actinomycin and ethionine. Starvation, cortisone, and triamcinolone were capable of inducing a pronounced increase in the incorporation of orotate into hepatic RNA. Actinomycin administration blocked the starvation- and steroid-induced rise in RNA specific activity. The glucocorticoid hormone induced increase in enzyme biosynthesis and the rise in free amino acid level were rapidly blocked by actinomycin and ethionine and were affected also by starvation.In the adaptation of the organism to acute starvation the hepatic enzyme-forming systems are regulated by the interplay of two hormones to produce a preferential maintenance of key gluconeogenic enzymes. Insulin, a suppressor of biosynthesis of gluconeogenic enzymes, is known to decrease in amount during starvation. Under the same circumstances glucocorticoid hormones, which are inducers of the biosynthesis of gluconeogenic enzymes, are present and thought to be responsible for the preferential maintenance of key gluconeogenic enzyme activities, thus ensuring adequate blood glucose levels in starvation.

scholarly journals Glucose transporter inhibitor-conjugated insulin mitigates hypoglycemia

2019 ◽  
Vol 116 (22) ◽  
pp. 10744-10748 ◽  
Author(s):  
Jinqiang Wang ◽  
Jicheng Yu ◽  
Yuqi Zhang ◽  
Anna R. Kahkoska ◽  
Zejun Wang ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Diabetic Mouse ◽  
Insulin Analog ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Uncontrolled Diabetes ◽  
Increased Risk

Insulin therapy in the setting of type 1 and advanced type 2 diabetes is complicated by increased risk of hypoglycemia. This potentially fatal complication could be mitigated by a glucose-responsive insulin analog. We report an insulin-facilitated glucose transporter (Glut) inhibitor conjugate, in which the insulin molecule is rendered glucose-responsive via conjugation to an inhibitor of Glut. The binding affinity of this insulin analog to endogenous Glut is modulated by plasma and tissue glucose levels. In hyperglycemic conditions (e.g., uncontrolled diabetes or the postprandial state), the in situ-generated insulin analog−Glut complex is driven to dissociate, freeing the insulin analog and glucose-accessible Glut to restore normoglycemia. Upon overdose, enhanced binding of insulin analog to Glut suppresses the glucose transport activity of Glut to attenuate further uptake of glucose. We demonstrate the ability of this insulin conjugate to regulate blood glucose levels within a normal range while mitigating the risk of hypoglycemia in a type 1 diabetic mouse model.

scholarly journals Deciphering the Roles of Thiazolidinediones and PPARγin Bladder Cancer

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Melody Chiu ◽  
Lucien McBeth ◽  
Puneet Sindhwani ◽  
Terry D. Hinds
Keyword(s):  
Bladder Cancer ◽  
De Novo ◽  
Diabetic Patients ◽  
Lipid Uptake ◽  
Potential Health ◽  
Protein Phosphatase 5 ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Bladder Cancer Cells ◽  
Patient Studies

The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPARγ, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively. Several studies have shown that PPARγ/TZDs decrease IGF-1 levels and, thus, reduce cancer growth in carcinomas such as the pancreas, colon, liver, and prostate. However, other studies have shed light on the potential of the receptor as a biomarker for uroepithelial carcinomas, particularly due to its stimulatory effect on migration of bladder cancer cells. Furthermore, PPARγmay provide the tumor-promoting microenvironment by de novo synthesis of nutrients that are needed for bladder cancer development. In this review, we closely examine the TZD class of drugs and their effects on PPARγin patient studies along with additional molecular factors that are positive modulators, such as protein phosphatase 5 (PP5), which may have considerable implications for bladder cancer therapy.

scholarly journals The Acute Biochemical Response of the Starved Rabbit Liver in Situ to Glucose Infusion

1974 ◽  
Vol 27 (3) ◽  
pp. 249
Author(s):  
JF Williams ◽  
MG Irving ◽  
PF Blackmore ◽  
HL Regtop ◽  
MG Clark
Keyword(s):  
Fatty Acids ◽  
Blood Glucose ◽  
Free Fatty Acids ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate ◽  
Rabbit Liver ◽  
Oxidative Pentose Phosphate Pathway ◽  
Glucose Levels ◽  
Blood Glucose Levels

Increasing the blood glucose levels from 88 to 400 mg/IOO ml in rabbit liver in situ during 5-min time intervals resulted in a decrease in the production of C02 from C-I of liver glucose together with a slight increase in the oxidation of C-6 of glucose; this was caused by a high glucose-induced decrease in the activity of the oxidative pentose phosphate pathway. Increasing the glucose concentrations also resulted in a threefold increase in the levels of palmitoyl- and stearoyl-CoA esters at a glucose load of 0�8 g; this is consistent with a specific feed-back inhibition of the production of NADPH by reactions of the oxidative pentose phosphate pathway by long-chain fatty acyl-CoAs. A decrease in plasma free fatty acids occurred when blood glucose levels were raised; this was associated with an increase in the concentration of free fatty acids in liver.

scholarly journals Hubungan aktivitas fisik dan obesitas sentral dengan hiperglikemia wanita dewasa: Cross-sectional study

2021 ◽  
Vol 6 (2) ◽  
pp. 199
Author(s):  
Bohari Bohari ◽  
Nuryani Nuryani ◽  
Rukman Abdullah ◽  
Lili Amaliah ◽  
Fahmi Hafid
Keyword(s):  
Physical Activity ◽  
Blood Glucose ◽  
Central Obesity ◽  
Activity Level ◽  
Adult Women ◽  
Activity Data ◽  
Cross Sectional ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels

Women in Indonesia are a group at risk of experiencing high blood glucose levels with increasing age. The purpose of the study was to analyze the relationship between physical activity and central obesity on hyperglycemia in adult women. The type of research is quantitative with a cross-sectional design on adult women at the Telaga Biru Public Health Center, Gorontalo Regency in 2019. The sample size is 248 people using purposive sampling. The method of collecting physical activity data is measured using a Physical Activity Level (PAL) questionnaire, central obesity is measuring waist circumference, and current blood glucose levels for hyperglycemic status. The statistical test is the chi-square test with 95% CI. The results showed that physical activity included in the light category was very high at 91.1% and central obesity status was also high at 61,3%. The results of current blood glucose levels showed that respondents who experienced hyperglycemia were low at only 15,3%. Physical activity had no significant association with hyperglycemia (p= 0,142), central obesity had a significant association with hyperglycemia (p= 0,005). The conclusion is that central obesity has a significant relationship with the incidence of hyperglycemia in adult women with an OR value of 3,52

scholarly journals Dioleoylphosphoethanolamine Retains Cell Surface GLUT4 by Inhibiting PKCα-Driven Internalization

2018 ◽  
Vol 46 (5) ◽  
pp. 1985-1998 ◽  
Author(s):  
Tomoyuki Nishizaki
Keyword(s):  
Cell Surface ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Surface Localization ◽  
Cell Surface Localization ◽  
Glucose Transporter Glut4

Background/Aims: Phosphatidylethanolamine, a component of the plasma membrane, regulates diverse cellular processes. The present study investigated the role of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in the trafficking of the glucose transporter GLUT4 and the glucose homeostasis. Methods: Monitoring of GLUT4 trafficking, GLUT4 internalization assay, and glucose uptake assay were carried out using differentiated 3T3-L1-GLUT4myc adipocytes. Akt1/2 and PKC isozymes were knocked-down by transfecting each siRNA. Cell-free PKC assay and in situ PKCα assay with a FRET probe were carried out. Oral glucose tolerance test (OGTT) was performed using BKS.Cg-+Lepdb/+Lebdb/Jcl mice, an animal model of type 2 diabetes mellitus (DM). Results: DOPE increased cell surface localization of the glucose transporter GLUT4 in differentiated 3T3-L1-GLUT4myc adipocytes, regardless of Akt activation. Likewise, PKCα deficiency increased cell surface localization of GLUT4, that occludes the effect of DOPE. DOPE clearly suppressed phorbol 12-myristate 13-acetate-induced PKCα activation in the cell-free and in situ PKC assay. DOPE and PKCα deficiency cancelled endocytic internalization of GLUT4 localized on the plasma membrane after insulin stimulation. DOPE significantly enhanced glucose uptake into cells. A similar effect was obtained by knocking-down PKCα, that occludes the effect of DOPE. In OGTT, oral administration with DOPE effectively restricted an increase in the blood glucose levels after glucose loading in type 2 DM model mice. Conclusion: The results of the present study show that DOPE retains cell surface GLUT4 by suppressing PKCα-driven endocytic internalization of GLUT4, to enhance glucose uptake into cells and restrict an increase in the blood glucose levels after glucose loading in type 2 DM.

Effects of Maternal Flaxseed Supplementation on Female Offspring of Diabetic Rats in Serum Concentration of Glucose, Insulin, and Thyroid Hormones

2019 ◽  
Vol 89 (1-2) ◽  
pp. 45-54
Author(s):  
Akemi Suzuki ◽  
André Manoel Correia-Santos ◽  
Gabriela Câmara Vicente ◽  
Luiz Guillermo Coca Velarde ◽  
Gilson Teles Boaventura
Keyword(s):  
Thyroid Hormones ◽  
High Fat Diet ◽  
Female Offspring ◽  
Flaxseed Oil ◽  
Diabetic Rats ◽  
High Fat ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Flaxseed Flour ◽  
Maternal Consumption

Abstract. Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (−31%), HFG (−33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (−10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.

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