Glucose and Insulin Metabolism in Cirrhosis

Author(s):  
Christopher O. Record
Keyword(s):  
1986 ◽  
Vol 111 (4) ◽  
pp. 516-521
Author(s):  
Nina Clausen ◽  
Per-Eric Lins ◽  
Ulf Adamson ◽  
Bertil Hamberger ◽  
Suad Efendić

Abstract. Hypothyroidism has been alleged to modulate insulin action and influence the secretion of growth hormone and catecholamines. We recently investigated the influence of hypothyroidism on glucose counterregulatory capacity and the hormonal responses to insulin-induced hypoglycaemia in 6 patients with primary hypothyroidism (age 32–52 years, TSH-values 66–200 mU/l). Hypoglycaemia was induced in the hypothyroid state and again when the subjects were euthyroid. After an overnight fast a constant rate infusion of insulin (2.4 U/h) was given for 4 h. Glucose was measured every 15 min and insulin, C-peptide, glucagon, epinephrine, norepinephrine, growth hormone and cortisol every 30 min for 5 h. During insulin infusion somewhat higher concentrations of the hormone were obtained in the hypothyroid state and simultaneously glucose levels were 0.5 mmol/l lower. As expected, basal norepinephrine levels were higher in hypothyroidism. However, no increase in circulating norepinephrine during hypoglycaemia was registered in the two experiments. The responses of counterregulatory hormones showed an enhanced response of cortisol, similar responses of growth hormone and epinephrine while the glucagon response was paradoxically impaired. Our findings suggest that hypothyroidism alters insulin metabolism, and that the glucagon response to hypoglycaemia is impaired in this condition.


2021 ◽  
Vol 9 (6) ◽  
pp. 1125
Author(s):  
Magloire Pandoua Nekoua ◽  
Antoine Bertin ◽  
Famara Sane ◽  
Jean-Pascal Gimeno ◽  
Isabelle Fournier ◽  
...  

Coxsackievirus-B4 (CV-B4) can persist in pancreatic cell lines and impair the phenoytpe and/or gene expressions in these cells; however, the models used to study this phenomenon did not produce insulin. Therefore, we investigated CV-B4 persistence and its consequences in insulin-producing pancreatic β cells. The insulin-secreting rat β cell line, INS-1, was infected with CV-B4. After lysis of a large part of the cell layer, the culture was still maintained and no additional cytopathic effect was observed. The amount of insulin in supernatants of cell cultures persistently infected with CV-B4 was not affected by the infection; in fact, a larger quantity of proinsulin was found. The mRNA expression of pro-hormone convertase 2, an enzyme involved in the maturation of proinsulin into insulin and studied using real-time reverse transcription-polymerase chain reaction, was inhibited in infected cultures. Further, the pattern of 47 cell proteins analyzed using Shotgun mass spectrometry was significantly modified. The DNA of persistently infected cell cultures was hypermethylated unlike that of controls. The persistent infection of INS-1 cells with CV-B4 had a deep impact on these cells, especially on insulin metabolism. Cellular changes caused by persistent CV-B4 infection of β cells can play a role in type 1 diabetes pathogenesis.


2021 ◽  
Vol 46 (6) ◽  
pp. 1350-1358
Author(s):  
Fruzsina Bagaméry ◽  
Kamilla Varga ◽  
Kitti Kecsmár ◽  
István Vincze ◽  
Éva Szökő ◽  
...  

AbstractRecently neuronal insulin resistance was suggested playing a role in Alzheimer’s disease. Streptozotocin (STZ) is commonly used to induce impairment in insulin metabolism. In our previous work on undifferentiated SH-SY5Y cells the compound exerted cytotoxicity without altering insulin sensitivity. Nevertheless, differentiation of the cells to a more mature neuron-like phenotype may considerably affect the significance of insulin signaling and its sensitivity to STZ. We aimed at studying the influence of STZ treatment on insulin signaling in SH-SY5Y cells differentiated by retinoic acid (RA). Cytotoxicity of STZ or low serum (LS) condition and protective effect of insulin were compared in RA differentiated SH-SY5Y cells. The effect of insulin and an incretin analogue, exendin-4 on insulin signaling was also examined by assessing glycogen synthase kinase-3 (GSK-3) phosphorylation. STZ was found less cytotoxic in the differentiated cells compared to our previous results in undifferentiated SH-SY5Y cells. The cytoprotective concentration of insulin was similar in the STZ and LS groups. However, the right-shifted concentration–response curve of insulin induced GSK-3 phosphorylation in STZ-treated differentiated cells is suggestive of the development of insulin resistance that was further confirmed by the insulin potentiating effect of exendin-4. Differentiation reduced the sensitivity of SH-SY5Y cells for the non-specific cytotoxicity of STZ and enhanced the relative significance of development of insulin resistance. The differentiated cells thus serve as a better model for studying the role of insulin signaling in neuronal survival. However, direct cytotoxicity of STZ also contributes to the cell death.


2021 ◽  
Vol 12 ◽  
pp. 204201882110121
Author(s):  
Jennifer L. Knopp ◽  
J. Geoffrey Chase ◽  
Geoffrey M. Shaw

Background: Critical care populations experience demographic shifts in response to trends in population and healthcare, with increasing severity and/or complexity of illness a common observation worldwide. Inflammation in critical illness impacts glucose–insulin metabolism, and hyperglycaemia is associated with mortality and morbidity. This study examines longitudinal trends in insulin sensitivity across almost a decade of glycaemic control in a single unit. Methods: A clinically validated model of glucose–insulin dynamics is used to assess hour–hour insulin sensitivity over the first 72 h of insulin therapy. Insulin sensitivity and its hour–hour percent variability are examined over 8 calendar years alongside severity scores and diagnostics. Results: Insulin sensitivity was found to decrease by 50–55% from 2011 to 2015, and remain low from 2015 to 2018, with no concomitant trends in age, severity scores or risk of death, or diagnostic category. Insulin sensitivity variability was found to remain largely unchanged year to year and was clinically equivalent (95% confidence interval) at the median and interquartile range. Insulin resistance was associated with greater incidence of high insulin doses in the effect saturation range (6–8 U/h), with the 75th percentile of hourly insulin doses rising from 4–4.5 U/h in 2011–2014 to 6 U/h in 2015–2018. Conclusions: Increasing insulin resistance was observed alongside no change in insulin sensitivity variability, implying greater insulin needs but equivalent (variability) challenge to glycaemic control. Increasing insulin resistance may imply greater inflammation and severity of illness not captured by existing severity scores. Insulin resistance reduces glucose tolerance, and can cause greater incidence of insulin saturation and resultant hyperglycaemia. Overall, these results have significant clinical implications for glycaemic control and nutrition management.


Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2236
Author(s):  
Navid Ghavipanje ◽  
Mohammad Hasan Fathi Nasri ◽  
Seyyed Homayoun Farhangfar ◽  
Seyyed Ehsan Ghiasi ◽  
Einar Vargas-Bello-Pérez

The objectives of this study were to evaluate the alleviating effects of the isoquinoline alkaloid berberine (BBR) on the energy balance (EB), glucose and insulin metabolism, and liver functionality in transition dairy goats, as reflected by blood metabolites and enzymes. Twenty-four primiparous Saanen goats were randomly allocated to four groups. Goats in each group received, ad libitum, the same basal diet during the pre- and post-partum periods of evaluation. Goats received daily0, 1, 2, or 4 g BBR (coded as CON, BBR1, BBR2, and BBR4, respectively). Dry matter intake (DMI) and milk yield were recorded daily. Blood samples were collected on days −21, −14, −7, 0, 7, 14, and 21 relative to kidding, and individual body condition scores (BCSs) were also recorded. Supplementation with either BBR2 or BBR4 increased (p < 0.05) pre- and post-partum DMI, increasing (p < 0.05) the intakes of net energy for lactating and metabolizable proteins. BBR2 and BBR4 increased (p < 0.05) post-partum milk production as well as fat-corrected milk (FCM), energy-corrected milk (ECM), and feed efficiency, indicating the alleviating effect of BBR on the negative energy balance (NEB) in transition goats. The daily ingestion of either 2 or 4 g BBR reduced (p < 0.05) plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and increased (p < 0.05) the dynamic change in the liver activity index (LAI) and liver functionality index (LFI), implying its hepatoprotective effect on transition goats. Overall, the results suggest that BBR supplementation of at least 2 g/d may help to ameliorate insulin resistance (IR) and fat metabolism disorders initiated by the NEB in transition dairy goats.


2016 ◽  
Vol 116 (8) ◽  
pp. 1394-1401 ◽  
Author(s):  
Shahnaz Ahmadi ◽  
Mehri Jamilian ◽  
Maryam Tajabadi-Ebrahimi ◽  
Parvaneh Jafari ◽  
Zatollah Asemi

AbstractTo the best of our knowledge, data on the effects of synbiotic supplementation on markers of insulin metabolism and lipid concentrations in patients with gestational diabetes mellitus (GDM) are scarce. The aim of the current study was to determine the effects of synbiotic supplementation on markers of insulin metabolism and lipid profiles in GDM patients. In total, seventy patients with GDM aged 18–40 years were assigned to two groups – the synbiotic group (n 35) and the placebo group (n 35) – in this randomised, double-blind, placebo-controlled trial. Patients in the synbiotic group received a daily capsule that contained three viable and freeze-dried strains: Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum (2×109 colony-forming units/g each) plus 800 mg inulin for 6 weeks. Fasting blood samples were collected at the beginning and week 6 to quantify related markers. After 6 weeks of intervention, compared with the placebo, synbiotic supplementation led to a significant decrease in serum insulin levels (−1·5 (sd 5·9) v. +4·8 (sd 11·5) µIU/ml, P=0·005), homoeostatic model assessment for insulin resistance (−0·4 (sd 1·3) v. +1·1 (sd 2·7), P=0·003) and homoeostatic model assessment for β cell function (−5·1 (sd 24·2) v. +18·9 (sd 45·6), P=0·008) and a significant increase in quantitative insulin sensitivity check index (+0·01 (sd 0·01) v. −0·007 (sd 0·02), P=0·02). In addition, synbiotic intake significantly decreased serum TAG (−14·8 (sd 56·5) v. +30·4 (sd 37·8) mg/dl, P<0·001) and VLDL-cholesterol concentrations (−3·0 (sd 11·3) v. +6·1 (sd 7·6) mg/dl, P<0·001) compared with the placebo. Overall, the results of this study demonstrate that taking synbiotic supplements for 6 weeks among patients with GDM had beneficial effects on markers of insulin metabolism, TAG and VLDL-cholesterol concentrations.


1977 ◽  
Vol 37 (2) ◽  
pp. 167-186 ◽  
Author(s):  
J. D. Wood ◽  
N. G. Gregory ◽  
G. M. Hall ◽  
D. Lister

1. Two experiments were done with Pietrain and Large White pigs (about 50 kg body-weight) to determine whether fat mobilization is enhanced in the stress-sensitive Pietrains (which also produce pale, soft, exudative (PSE) meat).2. In Expt 1, plasma glucose and insulin concentrations and free fatty acid (FFA) concentrations and composition were measured in five Pietrains and five Large Whites after feeding, during an infusion of norepinephrine (2.5 μg/kg body-weight per min), 16 and 21 h after the withdrawal of food and following insulin administration (0.3 IU/kg body-weight). The entry rate of oleic acid was measured 4 h after feeding. Body composition and longissimus dorsi pH measurements were made on killing the pigs 4 d after the experiment.3. After feeding, the Pietrains tended to have lower concentrations of glucose and insulin in plasma compared with the Large Whites, and higher concentrations of FFA. The Pietrains also had a faster entry rate of oleic acid into body tissues. In fasting (16 h) these differences in hormone and metabolite concentrations were also present and relationships between them and body development could be detected. Pietrains had higher concentrations of FFA and lower concentrations of insulin than Large Whites at a particular stage of the development of fat and muscle (subcutaneous fat weight÷longissimus muscle weight).4. The fatty acid composition of FFA resembled that of the backfat triglycerides in fasting and during norepinephrine infusion but not in the fed state. In particular the proportion of fatty acid 18:1 was low in the fed pigs and that of 18:2 was high. The contrast in FFA composition between the fed and stimulated state was greater in the Large Whites.5. The Pietrains were less sensitive to the antilipolytic action of insulin. Glucose and FFA concentrations were similar in both breeds during the norepinephrine infusion although insulin concentrations were increased to a larger extent in the Large Whites at the termination of the infusion.6. In Expt 2, anaesthetized Pietrain and Large White pigs were given constant infusions of norepinephrine alone (2.5 μg/kg body-weight per min) and norepinephrine+propranolol (2 and 10 μg/kg body-weight per min) or phentolamine (2 and 10 μg/kg body-weight per min). The aim was to determine whether the breeds differed in their sensitivity to norepinephrine when conscious responses to the hormone were prevented.7. When norepinephrine alone was infused, fat mobilization was greater in the Pietrain pigs and glucose concentrations were greater in the Large Whites. Propranolol markedly reduced the lipolytic action of norepinephrine, particularly in the Pietrain pigs studied, and phentolamine reduced its glycogenolytic action, particularly in the Large White pig.8. It seems that the leanness of stress-sensitive, PSE-susceptible Pietrain pigs may be due to an enhanced fat mobilization under various conditions, associated with an impairment in insulin metabolism and a greater sensitivity to the β-adrenergic action of catecholamines on body fat stores.


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