scholarly journals Computational Analysis of Insulin-Glucagon Signalling Network: Implications of Bistability to Metabolic Homeostasis and Disease states

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pramod R. Somvanshi ◽  
Manu Tomar ◽  
Venkatesh Kareenhalli
Keyword(s):  
Plasma Glucose ◽  
Positive Feedback ◽  
Metabolic Regulation ◽  
Metabolic Homeostasis ◽  
Glucose Levels ◽  
Disease States ◽  
Signalling Network ◽  
Catabolic Response ◽  
Low Glucose ◽  
Obesity And Cancer

Abstract Insulin and glucagon control plasma macronutrient homeostasis through their signalling network composed of multiple feedback and crosstalk interactions. To understand how these interactions contribute to metabolic homeostasis and disease states, we analysed the steady state response of metabolic regulation (catabolic or anabolic) with respect to structural and input perturbations in the integrated signalling network, for varying levels of plasma glucose. Structural perturbations revealed: the positive feedback of AKT on IRS is responsible for the bistability in anabolic zone (glucose >5.5 mmol); the positive feedback of calcium on cAMP is responsible for ensuring ultrasensitive response in catabolic zone (glucose <4.5 mmol); the crosstalk between AKT and PDE3 is responsible for efficient catabolic response under low glucose condition; the crosstalk between DAG and PKC regulates the span of anabolic bistable region with respect to plasma glucose levels. The macronutrient perturbations revealed: varying plasma amino acids and fatty acids from normal to high levels gradually shifted the bistable response towards higher glucose range, eventually making the response catabolic or unresponsive to increasing glucose levels. The analysis reveals that certain macronutrient composition may be more conducive to homeostasis than others. The network perturbations that may contribute to disease states such as diabetes, obesity and cancer are discussed.

scholarly journals Computational Analysis of Insulin-Glucagon Signalling Network: Implications of Bistability in Metabolic Homeostasis and Disease states

2019 ◽  
Author(s):  
Pramod R Somvanshi ◽  
Manu Tomar ◽  
Venkatesh Kareenhalli
Keyword(s):  
Plasma Glucose ◽  
Positive Feedback ◽  
Metabolic Regulation ◽  
Metabolic Homeostasis ◽  
Glucose Levels ◽  
Disease States ◽  
Signalling Network ◽  
Catabolic Response ◽  
Low Glucose ◽  
Obesity And Cancer

AbstractInsulin and glucagon control plasma macronutrient homeostasis through their signalling network composed of multiple feedback and crosstalk mechanisms. To understand how these interactions contribute to metabolic homeostasis and disease states, we analysed the steady state response of metabolic regulation (catabolic or anabolic) with respect to structural and input perturbations in the integrated signalling network, for varying levels of plasma glucose. Structural perturbations revealed: the positive feedback of AKT on IRS is responsible for the bistability in anabolic zone (glucose >5.5 mmol); the positive feedback of calcium on cAMP is responsible for ensuring ultrasensitive response in catabolic zone (glucose <4.5 mmol); the crosstalk between AKT and PDE3 is responsible for efficient catabolic response under low glucose condition; the crosstalk between DAG and PKC regulates the span of anabolic bistable region with respect to plasma glucose levels. The macronutrient perturbations revealed: varying plasma amino acids and fatty acids from normal to high levels gradually shifted the bistable response towards higher glucose range eventually making the response catabolic or unresponsive to increasing glucose levels. The analysis reveals that certain macronutrient composition may be more conducive to homeostasis than others. The network perturbations that may contribute to disease states such as diabetes, obesity and cancer are discussed.

scholarly journals Role for leptin in promoting glucose mobilization during acute hyperosmotic stress in teleost fishes

2013 ◽  
Vol 220 (1) ◽  
pp. 61-72 ◽  
Author(s):  
David A Baltzegar ◽  
Benjamin J Reading ◽  
Jonathon D Douros ◽  
Russell J Borski
Keyword(s):  
Amino Acid ◽  
Plasma Glucose ◽  
Metabolic Regulation ◽  
Leptin Receptor ◽  
Control Fish ◽  
Plasma Metabolites ◽  
Endocrine Regulation ◽  
Glucose Levels ◽  
Lactate Levels

Osmoregulation is critical for survival in all vertebrates, yet the endocrine regulation of this metabolically expensive process is not fully understood. Specifically, the function of leptin in the regulation of energy expenditure in fishes, and among ectotherms, in general, remains unresolved. In this study, we examined the effects of acute salinity transfer (72 h) and the effects of leptin and cortisol on plasma metabolites and hepatic energy reserves in the euryhaline fish, the tilapia (Oreochromis mossambicus). Transfer to 2/3 seawater (23 ppt) significantly increased plasma glucose, amino acid, and lactate levels relative to those in the control fish. Plasma glucose levels were positively correlated with amino acid levels (R2=0.614), but not with lactate levels. The mRNA expression of liver leptin A (lepa), leptin receptor (lepr), and hormone-sensitive and lipoprotein lipases (hslandlpl) as well as triglyceride content increased during salinity transfer, but plasma free fatty acid and triglyceride levels remained unchanged. Both leptin and cortisol significantly increased plasma glucose levelsin vivo, but only leptin decreased liver glycogen levels. Leptin decreased the expression of liverhslandlplmRNAs, whereas cortisol significantly increased the expression of these lipases. These findings suggest that hepatic glucose mobilization into the blood following an acute salinity challenge involves both glycogenolysis, induced by leptin, and subsequent gluconeogenesis of free amino acids. This is the first study to report that teleost leptin A has actions that are functionally distinct from those described in mammals acting as a potent hyperglycemic factor during osmotic stress, possibly in synergism with cortisol. These results suggest that the function of leptin may have diverged during the evolution of vertebrates, possibly reflecting differences in metabolic regulation between poikilotherms and homeotherms.

scholarly journals Sequence and expression analysis of glucokinase mRNA from herbivorous Giant gourami (Osphronemus goramy)

2021 ◽  
Vol 22 (2) ◽  
Author(s):  
Dian Novita Sari ◽  
Hasan Nasrullah ◽  
Julie Ekasari ◽  
Muhammad Agus Suprayudi ◽  
Alimuddin Alimuddin
Keyword(s):  
Expression Analysis ◽  
Plasma Glucose ◽  
High Glucose ◽  
Metabolic Regulation ◽  
Mrna Level ◽  
Amino Acid Sequences ◽  
Mrna Sequence ◽  
Glucose Levels ◽  
Glucose Injection ◽  
Pcr Method

Abstract. Sari DN, Nasrullah H, Ekasari J, Suprayudi MA, Alimuddin A. 2021. Sequence and expression analysis of glucokinase mRNA from herbivorous Giant gourami (Osphronemus goramy). Biodiversitas 22: 741-750. Glucokinase (GCK) is one of the enzymes that play important roles in carbohydrate metabolism and high glucose homeostatic in fish. The information about the GCK mRNA sequence and its expression is limited in Giant gourami, one of the most important herbivorous aquaculture species in Indonesia. The present study aimed to characterize the GCK mRNA and analyze its mRNA expression and plasma glucose levels after high glucose injection in Giant gourami. We also compared its sequence variability among carnivorous and herbivorous fish. The GCK mRNA was identified using polymerase chain reaction (PCR) method from the fish liver. Its mRNA level was analyzed by real-time PCR (qPCR). Giant gourami GCK mRNA sequence was 2104 nucleotide long, encoding 478 amino acids, and shared high similarity with other fish. GCK was mainly expressed in the liver. The mRNA level of GCK was highly up-regulated after 6 hours of high glucose injection, in-line with the plasma glucose in the blood. There are no major differences observed in the GCK amino acid sequences among Giant gourami and other fish. The knowledge gained from this study could be used as a reference for further exploration of metabolic regulation in Giant gourami.

Defective glucoregulation of brain alpha 2-adrenoceptors in obesity-prone rats

1993 ◽  
Vol 264 (2) ◽  
pp. R305-R311 ◽  
Author(s):  
B. E. Levin ◽  
B. Planas
Keyword(s):  
Plasma Glucose ◽  
High Energy ◽  
Hypothalamic Nucleus ◽  
Plasma Norepinephrine ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Low Glucose ◽  
Positive Correlations

Only half the male Sprague-Dawley rats fed high-energy diets develop diet-induced obesity (DIO); the rest are diet resistant (DR). It has been established that rats prone to develop DIO have decreased basal brain alpha 2-adrenoceptor levels compared with DR-prone rats and that DIO- but not DR-prone rats show glucose-induced increases in plasma norepinephrine (NE) levels. Because it has also been shown that alpha 2-adrenoceptors modulate ingestive and autonomic functions and are responsive to changes in plasma glucose levels, we tested the hypothesis that DIO- and DR-prone rats would regulate these receptors differently by using hyperinsulinemic clamping to vary plasma glucose levels. Rats with low glucose-induced plasma NE responses (DR-prone) showed significant positive correlations (r = 0.724-0.919) between plasma glucose levels and alpha 2-adrenoceptor ([3H]paraminoclonidine) binding in 5 of 17 brain areas (anterior, ventromedial, and arcuate hypothalamic nucleus; medial and basomedial amygdalar nucleus) assessed by autoradiographic techniques. Near-significant correlations were also seen in the paraventricular nucleus and lateral hypothalamus. High glucose-induced NE responders (DIO-prone) showed such a correlation only in the arcuate nucleus (r = 0.726). There was little glucoregulation of alpha 1-adrenoceptors. The defective ability of DIO-prone rats to alter brain alpha 2-adrenoceptors to changes in plasma glucose levels might underlie their predisposition to become obese on diets high in sucrose.

Effect of High ß-Glucan Barley on Postprandial Plasma Glucose Levels in Subjects with Normal Glucose Tolerance and Patients with Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 772-P
Author(s):  
MARIKO HIGA ◽  
AYANA HASHIMOTO ◽  
MOE HAYASAKA ◽  
MAI HIJIKATA ◽  
AYAMI UEDA ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Normal Glucose Tolerance ◽  
Postprandial Plasma Glucose ◽  
Glucose Levels ◽  
Normal Glucose

Effect of Fetal and Neonatal Hypothyroidism on Glucose Tolerance in Middle-Aged Female Rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Sajad Jeddi ◽  
Saeedeh Khalifi ◽  
Mahboubeh Ghanbari ◽  
Asghar Ghasemi
Keyword(s):  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Female Offspring ◽  
Female Rats ◽  
Control Group ◽  
Female Rat ◽  
Middle Aged ◽  
Intravenous Glucose ◽  
Neonatal Hypothyroidism ◽  
Glucose Levels

Background and objective: The effects of hypothyroidism during pregnancy and lactation on carbohydrate metabolism have been mostly studied in male animals. The aim of this study is therefore to investigate effect of fetal and neonatal hypothyroidism (FH and NH) on the glucose tolerance in middle-aged female rat offspring. Methods: Pregnant female rats were divided into three groups: Rats in the control group consumed tap water, while those in the FH and NH groups consumed 250 mg/L of 6-propyl-2-thiouracil (PTU) in their drinking water during gestation or lactation periods, respectively. After weaning, the female offspring were separated and divided into 3 groups (n=8/group): Control, FH, and NH. Body weight was recorded monthly and intravenous glucose tolerance test (IVGTT) was performed at month 12. Results: Compared to controls, female rats in the FH group had significantly higher plasma glucose levels than controls throughout the IVGTT except at min 60. Values at min 5 of the FH and control group were 196.1±1.9 and 155.3±5.9 mg/dL, respectively (P<0.05). In the NH group, plasma glucose levels were significantly higher only at min 5 (185.7±14.1 vs. 155.3±5.9 mg/dL, P<0.05). Conclusion: Hypothyroidism during fetal or neonatal periods caused glucose intolerance in middle-aged female offspring rats.

scholarly journals Prevention of Postprandial Hyperglycemia by Ophthalmic Nanoparticles Based on Protamine Zinc Insulin in the Rabbit

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 375
Author(s):  
Saori Deguchi ◽  
Fumihiko Ogata ◽  
Takumi Isaka ◽  
Hiroko Otake ◽  
Yosuke Nakazawa ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Plasma Glucose ◽  
Polyacrylic Acid ◽  
Rabbit Model ◽  
Postprandial Hyperglycemia ◽  
Postprandial Blood Glucose ◽  
Oral Glucose ◽  
Glucose Levels ◽  
Protamine Zinc Insulin ◽  
Bead Mill

Postprandial hyperglycemia, a so-called blood glucose spike, is associated with enhanced risks of diabetes mellitus (DM) and its complications. In this study, we attempted to design nanoparticles (NPs) of protamine zinc insulin (PZI) by the bead mill method, and prepare ophthalmic formulations based on the PZI-NPs with (nPZI/P) or without polyacrylic acid (nPZI). In addition, we investigated whether the instillation of the newly developed nPZI and nPZI/P can prevent postprandial hyperglycemia in a rabbit model involving the oral glucose tolerance test (OGTT). The particle size of PZI was decreased by the bead mill to a range for both nPZI and nPZI/P of 80–550 nm with no observable aggregation for 6 d. Neither nPZI nor nPZI/P caused any noticeable corneal toxicity. The plasma INS levels in rabbits instilled with nPZI were significantly higher than in rabbits instilled with INS suspensions (commercially available formulations, CA-INS), and the plasma INS levels were further enhanced with the amount of polyacrylic acid in the nPZI/P. In addition, the rapid rise in plasma glucose levels in OGTT-treated rabbits was prevented by a single instillation of nPZI/P, which was significantly more effective at attenuating postprandial hyperglycemia (blood glucose spike) in comparison with nPZI. In conclusion, we designed nPZI/P, and show that a single instillation before OGTT attenuates the rapid enhancement of plasma glucose levels. These findings suggest a better management strategy for the postprandial blood glucose spike, which is an important target of DM therapy.

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