Acromegaly and insulin resistance: a case study

1986 ◽  
Vol 111 (4) ◽  
pp. 445-451 ◽  
Author(s):  
J. M. Garía López ◽  
A. De La Fuente ◽  
Ma A. Tomé ◽  
J. A. Mato Mato ◽  
G. Juan Gaudiero ◽  
...  

Abstract. Elevated levels of growth hormone (GH) alter both the glucose tolerance and the sensitivity of peripheral tissue to insulin. We have studied the relationship between impaired glucose metabolism and its variations with different plasma levels of endogenous GH in one patient with acromegaly. To do so, we studied the decline in blood glucose concentration, as induced by iv insulin infusion, from a given hyperglycaemic level. With high levels of GH (GH = 120 μg/l), the slope of the straight line representing the decrease in blood glucose after insulin infusion was —0.71, the time required to achieve normoglycaemic levels, 270 min, and the corrected area under the curve representing blood glucose 26070 units2. After 10 months' bromocriptine treatment, GH plasma concentration fell to 8 μg/l, at which point the slope of the straight line was —1.40, the time required to achieve normoglycaemic levels 115 min, and the area under the curve 8956 units2. There was a greater total clearance of glucose when GH levels were lower (1.90 vs 1.00 ml/min/kg), as well as greater elimination of glucose from the extracellular glucose pool (4.02 vs 1.67 mg/min/kg). In conclusion, in this patient the elevated plasma levels of endogenous GH induced insulin resistance. Once GH levels were reduced by the administration of bromocriptine, glucose metabolism improved.

2014 ◽  
Vol 307 (4) ◽  
pp. H587-H597 ◽  
Author(s):  
Mark W. Sims ◽  
James Winter ◽  
Sean Brennan ◽  
Robert I. Norman ◽  
G. André Ng ◽  
...  

While it is well established that mortality risk after myocardial infarction (MI) increases in proportion to blood glucose concentration at the time of admission, it is unclear whether there is a direct, causal relationship. We investigated potential mechanisms by which increased blood glucose may exert cardiotoxicity. Using a Wistar rat or guinea-pig isolated cardiomyocyte model, we investigated the effects on cardiomyocyte function and electrical stability of alterations in extracellular glucose concentration. Contractile function studies using electric field stimulation (EFS), patch-clamp recording, and Ca2+ imaging were used to determine the effects of increased extracellular glucose concentration on cardiomyocyte function. Increasing glucose from 5 to 20 mM caused prolongation of the action potential and increased both basal Ca2+ and variability of the Ca2+ transient amplitude. Elevated extracellular glucose concentration also attenuated the protection afforded by ischemic preconditioning (IPC), as assessed using a simulated ischemia and reperfusion model. Inhibition of PKCα and β, using Gö6976 or specific inhibitor peptides, attenuated the detrimental effects of glucose and restored the cardioprotected phenotype to IPC cells. Increased glucose concentration did not attenuate the cardioprotective role of PKCε, but rather activation of PKCα and β masked its beneficial effect. Elevated extracellular glucose concentration exerts acute cardiotoxicity mediated via PKCα and β. Inhibition of these PKC isoenzymes abolishes the cardiotoxic effects and restores IPC-mediated cardioprotection. These data support a direct link between hyperglycemia and adverse outcome after MI. Cardiac-specific PKCα and β inhibition may be of clinical benefit in this setting.


Author(s):  
Ying Zhao ◽  
Yan Shu ◽  
Ning Zhao ◽  
Zili Zhou ◽  
Xiong Jia ◽  
...  

Long-term sleep deprivation (SD) is a bad lifestyle habit, especially among specific occupational practitioners, characterized by circadian rhythm misalignment and abnormal sleep/wake cycles. SD is closely associated with an increased risk of metabolic disturbance, particularly obesity and insulin resistance. The incretin hormone, glucagon-like peptide-1 (GLP-1), is a critical insulin release determinant secreted by the intestinal L-cell upon food intake. Besides, the gut microbiota participates in metabolic homeostasis and regulates GLP-1 release in a circadian rhythm manner. As a commonly recognized intestinal probiotic, Bifidobacterium has various clinical indications regarding its curative effect. However, few studies have investigated the effect of Bifidobacterium supplementation on sleep disorders. In the present study, we explored the impact of long-term SD on the endocrine metabolism of rhesus monkeys and determined the effect of Bifidobacterium supplementation on the SD-induced metabolic status. Lipids concentrations, body weight, fast blood glucose, and insulin levels increased after SD. Furthermore, after two months of long-term SD, the intravenous glucose tolerance test (iVGTT) showed that the glucose metabolism was impaired and the insulin sensitivity decreased. Moreover, one month of Bifidobacterium oral administration significantly reduced blood glucose and attenuated insulin resistance in rhesus macaques. Overall, our results suggested that Bifidobacterium might be used to alleviate SD-induced aberrant glucose metabolism and improve insulin resistance. Also, it might help in better understanding the mechanisms governing the beneficial effects of Bifidobacterium.


Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 754
Author(s):  
Karah J. Dring ◽  
Simon B. Cooper ◽  
Ryan A. Williams ◽  
John G. Morris ◽  
Caroline Sunderland ◽  
...  

High-intensity intermittent exercise (HIIE) is a potential intervention to manage hyperglycaemia and insulin resistance in adolescents. The aim of this study was to determine the optimum duration of HIIE to reduce postprandial glycaemic and insulinaemic responses in adolescents and the longevity of the response. Thirty-nine participants (12.4 ± 0.4 year) completed a 30- and 60-min exercise trial (Loughborough Intermittent Shuttle Test) and a rested control trial in a randomised crossover design. Capillary blood samples were taken at baseline, immediately and 1-h post-exercise; and 30, 60 and 120 min following a standardised lunch (day one) and a standardised breakfast 24-h post-exercise. Plasma insulin total area under the curve (tAUC) following lunch was lower following 60-min HIIE (21,754 ± 16,861 pmol·L−1 × 120 min, p = 0.032) and tended to be lower following 30-min HIIE (24,273 ± 16,131 pmol·L−1 × 120 min, p = 0.080), when compared with the resting condition (26,931 ± 21,634 pmol·L−1 × 120 min). Blood glucose concentration was lower 1-h post-exercise following 30-min HIIE (3.6 ± 0.6 mmol·L−1) when compared to resting (4.1 ± 0.9 mmol·L−1, p = 0.001). Blood glucose and plasma insulin concentration did not differ across trials on day two. Shorter bouts of HIIE (30-min), as well as a 60-min bout, reduced the postprandial insulinaemic response to lunch, an ecologically valid marker of insulin sensitivity. As the beneficial effects of HIIE were limited to 3 h post-exercise, adolescents are recommended to engage daily HIIE to enhance metabolic health.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4166 ◽  
Author(s):  
Mohamed R. Ben Khedher ◽  
Mohamed Hammami ◽  
Jonathan R.S. Arch ◽  
David C. Hislop ◽  
Dominic Eze ◽  
...  

Background Salvia officinalis (sage) is a native plant to the Mediterranean region and has been used for a long time in traditional medicine for various diseases. We investigated possible anti-diabetic, anti-inflammatory and anti-obesity effects of sage methanol (MetOH) extract in a nutritional mouse model of obesity, inflammation and insulin resistance, as well as its effects on lipolysis and lipogenesis in 3T3-L1 cells. Methods Diet-induced obese (DIO) mice were treated for five weeks with sage methanol extract (100 and 400 mg kg−1/day bid), or rosiglitazone (3 mg kg−1/day bid), as a positive control. Energy expenditure, food intake, body weight, fat mass, liver glycogen and lipid content were evaluated. Blood glucose, and plasma levels of insulin, lipids leptin and pro- and anti-inflammatory cytokines were measured throughout the experiment. The effects of sage MetOH extract on lipolysis and lipogenesis were tested in vitro in 3T3-L1 cells. Results After two weeks of treatment, the lower dose of sage MetOH extract decreased blood glucose and plasma insulin levels during an oral glucose tolerance test (OGTT). An insulin tolerance test (ITT), performed at day 29 confirmed that sage improved insulin sensitivity. Groups treated with low dose sage and rosiglitazone showed very similar effects on OGTT and ITT. Sage also improved HOMA-IR, triglycerides and NEFA. Treatment with the low dose increased the plasma levels of the anti-inflammatory cytokines IL-2, IL-4 and IL-10 and reduced the plasma level of the pro-inflammatory cytokines IL-12, TNF-α, and KC/GRO. The GC analysis revealed the presence of two PPARs agonist in sage MetOH extract. In vitro, the extract reduced in a dose-related manner the accumulation of lipid droplets; however no effect on lipolysis was observed. Conclusions Sage MetOH extract at low dose exhibits similar effects to rosiglitazone. It improves insulin sensitivity, inhibits lipogenesis in adipocytes and reduces inflammation as judged by plasma cytokines. Sage presents an alternative to pharmaceuticals for the treatment of diabetes and associated inflammation.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Caiping Lu ◽  
Hanying Xing ◽  
Linquan Yang ◽  
Kaiting Chen ◽  
Linyi Shu ◽  
...  

Diabetes mellitus is highly prevalent worldwide. High-fat-diet (HFD) consumption can lead to liver fat accumulation, impair hepatic glycometabolism, and cause insulin resistance and the development of diabetes. Resveratrol has been shown to improve the blood glucose concentration of diabetic mice, but its effect on the abnormal hepatic glycometabolism induced by HFD-feeding and the mechanism involved are unknown. In this study, we determined the effects of resveratrol on the insulin resistance of high-fat-diet-fed mice and a hepatocyte model by measuring serum biochemical indexes, key indicators of glycometabolism, glucose uptake, and glycogen synthesis in hepatocytes. We found that resveratrol treatment significantly ameliorated the HFD-induced abnormalities in glucose metabolism in mice, increased glucose absorption and glycogen synthesis, downregulated protein phosphatase 2A (PP2A) and activated Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ), and increased the phosphorylation of AMP-activated protein kinase (AMPK). In insulin-resistant HepG2 cells, the administration of a PP2A activator or CaMKKβ inhibitor attenuated the effects of resveratrol, but the administration of an AMPK inhibitor abolished the effects of resveratrol. Resveratrol significantly ameliorates abnormalities in glycometabolism induced by HFD-feeding and increases glucose uptake and glycogen synthesis in hepatocytes. These effects are mediated through the activation of AMPK by PP2A and CaMKKβ.


2016 ◽  
Vol 9 (4) ◽  
pp. 177
Author(s):  
A. S. M. Zakaria ◽  
Md. Kamal Hossain ◽  
Mohammed Saiful Islam Bhuiyan ◽  
Abida Sultana ◽  
Mahmudur Rahman ◽  
...  

<p>The aim of this study was to see the association of lichen planus (n=80) with glucose metabolism disturbance. Classic variety of lichen planus was the most common (76.3%), followed by ashy dermatosis, hypertrophic, oral, actinic and nail lichen planus. The blood glucose level 2 hours after glucose drink was abnormal in 20 cases. HbA<sub>1</sub>c was abnormal in 7 cases. The mean homeostasis model of assessment formulation- insulin resistance index (HOMA-IR) was 2.1 ± 1.6 and it was higher (&gt;4.8) in 12.5% patients. Diabetes mellitus was found in 30 patients. Impaired glucose tolerance was found in 15 cases and high HOMA-IR was found in 10 cases. Total number of cases of abnormal glucose metabolism was found in 55 (68.8%) cases of lichen planus. In conclusion, patients with lichen planus  have higher risk of abnormal glucose metabolism specially diabetes mellitus.</p>


2017 ◽  
Vol 4 (5) ◽  
pp. e378 ◽  
Author(s):  
Myla D. Goldman ◽  
Scott Koenig ◽  
Casey Engel ◽  
Christopher R. McCartney ◽  
Min-Woong Sohn

Objective:To determine the relationship between MS relapse recovery and blood glucose (BG) response to IV methylprednisolone (IVMP) treatment.Methods:We retrospectively identified 36 patients with MS admitted for IVMP treatment of acute relapse who had adequate data to characterize BG response, relapse severity, and recovery. The relationship between glucocorticoid-associated nonfasting BG (NFBG) and relapse recovery was assessed.Results:Highest recorded nonfasting BG (maximum NFBG [maxNFBG]) values were significantly higher in patients with MS without relapse recovery compared with those with recovery (271 ± 68 vs 209 ± 48 mg/dL, respectively; p = 0.0045). After adjusting for relapse severity, MS patients with maxNFBG below the group median were 6 times (OR = 6.01; 95% CI, 1.08–33.40; p = 0.040) more likely to experience relapse recovery than those with maxNFBG above the group median. In a multiple regression model adjusting for age, sex, and relapse severity, a 1-mg/dL increase in the maxNFBG was associated with 4.5% decrease in the probability of recovery (OR = 0.955; 95% CI, 0.928–0.983; p = 0.002).Conclusions:These findings suggest that higher glucocorticoid-associated NFBG values in acutely relapsing patients with MS are associated with diminished probability of recovery. This relationship could reflect steroid-associated hyperglycemia and/or insulin resistance, defects in non–steroid-associated (e.g., prerelapse) glucose metabolism, or both. This study included only those admitted for an MS relapse, and it is this subset of patients for whom these findings may be most relevant. A prospective study to evaluate glucose regulation and MS relapse recovery in a broader outpatient MS population is under way.


2016 ◽  
Vol 30 (4) ◽  
pp. 468-475 ◽  
Author(s):  
Megan M. Moore ◽  
Abby M. Bailey ◽  
Alexander H. Flannery ◽  
Regan A. Baum

Rabson-Mendenhall syndrome is a rare genetic disorder resulting from mutations in the insulin receptor and is associated with high degrees of insulin resistance. These patients are prone to complications secondary to their hyperglycemia including diabetic ketoacidosis (DKA). We report the case of a 19-year-old male with Rabson-Mendenhall syndrome presenting with DKA who required doses of up to 500 U/h (10.6 U/kg/h) of insulin. The patient’s insulin infusion was originally compounded with U-100 regular insulin, although to minimize volume, the product was compounded with U-500 insulin. The DKA eventually resolved requiring infusion rates ranging from 400 to 500 U/h. Although numerous opportunities for medication errors exist with the use of U-500 insulin, this case outlines the safe use of concentrated intravenous insulin when clinically indicated for patients requiring extremely high doses of insulin to control blood glucose.


Author(s):  
Dana N. Wright ◽  
Kondwani G.H. Katundu ◽  
Jose A. Viscarra ◽  
Daniel E. Crocker ◽  
John W. Newman ◽  
...  

The prolonged, post-weaning fast of northern elephant seal (Mirounga angustirostris) pups is characterized by a reliance on lipid metabolism and reversible, fasting-induced insulin resistance providing a unique model to examine the effects of insulin on lipid metabolism. We have previously shown that acute insulin infusion induced a shift in fatty acid metabolism dependent on fasting duration. This study complements the previous study by examining the effects of fasting duration and insulin infusion on circulating levels of oxylipins, bioactive metabolites derived from the oxygenation of polyunsaturated fatty acids. Northern elephant seal pups were studied at two post-weaning periods (n = 5/period): early fasting (1-2 weeks post-weaning; 127 ± 1 kg) and late fasting (6-7 weeks post-weaning; 93 ± 4 kg). Different cohorts of pups were weighed, sedated, and infused with 65 mU/kg of insulin. Plasma was collected prior to infusion (T0), and at 10, 30, 60, and 120 min post-infusion. A profile of ~80 oxylipins were analyzed by UPLC-ESI-MS/MS. Nine oxylipins changed between early and late fasting and eight were altered in response to insulin infusion. Fasting decreased PGF2a and increased 14,15-DiHETrE, 20-HETE, and 4-HDoHE (p<0.03) in T0 samples, while insulin infusion resulted in an inverse change in area under the curve (AUC) levels in these same metabolites (p<0.05). In addition, 12-HpETE and 12-HETE decreased with fasting and insulin infusion, respectively (p<0.04). The oxylipins altered during fasting and in response to insulin infusion may contribute to the manifestation of insulin resistance and participate in the metabolic regulation of associated cellular processes.


2017 ◽  
Vol 1 (1) ◽  
pp. 3
Author(s):  
Imran Khan

Background/objective: Medicinal plants including Stevia and Moringa constitute an important source of health-beneficial bioactive components and hence, their intake may beneficially modulate biomarkers of chronic diseases. Therefore, the objective of the present study was to investigate the effect of cookies incorporating stevia and Moringa leaf powder on postprandial glycaemia, appetite, palatability and       gastrointestinal wellbeing in humans. Design and methods: In a randomized   crossover design, twenty healthy subjects consumed three iso-caloric test foods (each providing 50 g available carbohydrates) of control cookies (CC), stevia leaf-containing cookies (SC) and Moringa leaf-containing cookies (MC) as breakfast. Blood glucose and subjective appetite were measured at fasting and over 2 hours after consumption of the cookies. Palatability and gastrointestinal wellbeing were measured using standard questionnaires. Results: Compared to CC, MC resulted in a significant  decrease in postprandial blood glucose concentration at 30 and 45 min (P = 0.002 and P = 0.003, respectively) and showed a tendency (P = 0.077) for lower blood glucose incremental area under the curve (iAUC). Subjects were significantly less hungry  after SC and MC intake (P= 0.035 and P= 0.041, respectively) compared to CC. In addition, the SC resulted in significantly (P = 0.037) lower hunger incremental area over the curve (iAOC) compared to CC. All the cookies were liked by the subjects without any reported gastrointestinal discomfort. Conclusion: In conclusion, the  results showed that compared to CC, MC improved postprandial glycaemia and reduced hunger, while SC reduced hunger only. Future studies are now warranted to explore the mechanisms responsible for these observed effects.


Sign in / Sign up

Export Citation Format

Share Document