Reduced Inhibitory Effect of Somatostatin on the Exocrine Function of the Pancreas and on Serum Insulin (IRI) Levels in Chronic Relapsing Pancreatitis

BACKGROUND/AIM: Our previous studies showed that administration of dexamethasone plus food increased serum leptin levels 100% more than dexamethasone alone. We hypothesized that this increase in leptin from the meal could result directly from the provision of fuel metabolites rather than from the meal-induced rise in insulin. In the current study, we tested the effect of an i.v. lipid fuel source (Intralipid 20%/heparin) that would incur only a modest increase in insulin. This study was undertaken because the role of lipid in the regulation of human leptin levels has been controversial, with differing effects reported: stimulatory, inhibitory, or no effect at all. METHODS: In order to evaluate how lipids affect serum leptin in humans, we administered the following to seven lean, healthy, fasting subjects: (i) Intralipid 20% at 0.83 ml/kg.h plus heparin (800 IE/h) infused i.v. for 7 h (LIPID), (ii) LIPID with one initial pulse of insulin (0.09 U/kg) given s.c. (LIPID+INS), (iii) LIPID with dexamethasone (2 mg i.v. push) given at the start of the infusion (LIPID+DEX), and (iv) LIPID with insulin plus dexamethasone (LIPID+INS+DEX). Control trials in another 14 subjects matched hormonal conditions but lacked the LIPID infusion. Blood levels were collected over 8 h for determination of free fatty acids (FFA), glucose, insulin, and leptin under each experimental condition. RESULTS: Over the 420 min of LIPID infusion, FFA levels rose four-fold from 0.28+/-0.05 mmol/l to 0.99+/-0.05 mmol/l. Serum leptin levels were suppressed by 10-20% in the LIPID condition as compared with control (no LIPID) between 90 min (P=0.008) and 360 min (P=0.045). LIPID+DEX did not increase leptin. A pulse of insulin (INS) increased serum insulin levels to 49.9+/-6.1 U/ml at 90 min and increased serum leptin by 21.3+/-6.6% at 480 min (P=0.054). LIPID decreased leptin in the face of this insulin-induced increase (LIPID+INS), between 360 min (P=0.017) and 420 min (P=0.003), with a 23% suppressive effect at 420 min. LIPID+DEX elevated leptin levels by 112.5+/-35.8% at 480 min (P=0.037), however, the Intralipid/heparin infusion did not blunt the rise of leptin under these conditions. CONCLUSIONS: These data showed that Intralipid/heparin: (i) are not sufficient to trigger the effect of dexamethasone on leptin, (ii) have an acute inhibitory effect on both fasting and insulin-stimulated leptin levels, and (iii) that this inhibitory effect cannot reverse the strong stimulatory effect of dexamethasone and insulin on serum leptin.

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Fenugreek Seed Extract Inhibit Fat Accumulation and Ameliorates Dyslipidemia in High Fat Diet-Induced Obese Rats

BioMed Research International ◽

10.1155/2014/606021 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 24

Author(s):

Parveen Kumar ◽

Uma Bhandari ◽

Shrirang Jamadagni

Keyword(s):

High Fat Diet ◽

Body Weight Gain ◽

Serum Insulin ◽

Fatty Acid Synthetase ◽

Thiobarbituric Acid ◽

Inhibitory Effect ◽

High Fat ◽

Lipid Digestion ◽

Fat Accumulation ◽

Obese Rats

This study investigated the inhibitory effect of aqueous extract ofTrigonella foenum-graecumseeds (AqE-TFG) on fat accumulation and dyslipidemia in high fat diet- (HFD-) induced obese rats. Female Wistar rats were fed with HFDad libitum, and the rats on HFD were treated orally with AqE-TFG or orlistat ((HFD for 28 days + AqE-TFG (0.5 and 1.0 g/kg) or orlistat (10 mg/kg) from day 8 to 28), respectively. Treatment with AqE-TFG produced significant reduction in body weight gain, body mass index (BMI), white adipose tissue (WAT) weights, blood glucose, serum insulin, lipids, leptin, lipase, and apolipoprotein-B levels and elevation in adiponectin levels. AqE-TFG improved serum aspartate amino transferase (AST), alanine amino transferase (ALT), and lactate dehydrogenase (LDH) levels. AqE-TFG treatment reduced the hepatic and cardiac thiobarbituric acid reactive substances (TBARS) and elevated the antioxidant enzyme (glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) levels. In addition, liver and uterine WAT lipogenic enzyme (fatty acid synthetase (FAS) and glucose-6-phosphate dehydrogenase (G6PD)) activities were restored towards normal levels. These findings demonstrated the preventive effect of AqE-TFG on fat accumulation and dyslipidemia, due to inhibition of impaired lipid digestion and absorption, in addition to improvement in glucose and lipid metabolism, enhancement of insulin sensitivity, increased antioxidant defense, and downregulation of lipogenic enzymes.

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Inverse association between serum insulin and sex hormone-binding globulin in a population survey in Sweden

Endocrine Connections ◽

10.1530/ec-12-0057 ◽

2013 ◽

Vol 2 (1) ◽

pp. 18-22 ◽

Cited By ~ 26

Author(s):

Bledar Daka ◽

Thord Rosen ◽

Per Anders Jansson ◽

Lennart Råstam ◽

Charlotte A Larsson ◽

...

Keyword(s):

Serum Insulin ◽

Inhibitory Effect ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Oral Glucose ◽

Inverse Association ◽

Hormone Binding ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Low Levels

Objectives Obesity is associated with low levels of sex hormone-binding globulin (SHBG). While the reason is not fully understood, we aimed to study the association between serum insulin and levels of SHBG in a random population. Design and methods Between 2001 and 2005, a random sample of 2816 participants aged 30–74 years were enrolled in a cross-sectional survey in the South-west of Sweden. Fasting blood samples were collected and an oral glucose tolerance test (OGTT) was conducted in all subjects without known diabetes. Diabetes mellitus was defined according to criteria from WHO, and clinical characteristics were used to discriminate between type 1 (T1D) and type 2 diabetes (T2D). Analyses of SHBG were successful in 2782 participants (98%), who thus constituted the current study population. Results We found significant inverse association between levels of SHBG and fasting serum insulin in both genders (men: β=−0.090, P=0.001; women: β=−0.197, P<0.001), which was independent of differences in age and BMI. The associations remained when also differences in fasting plasma glucose were accounted for (men: β=−0.062, P=0.022; women: β=−0.176, P≤0.001). Subjects with T1D exhibited higher levels of SHBG than both T2D (men: δ=15.9 nmol/l, P<0.001; women: δ=71.1 nmol/l, P<0.001) and non-diabetic subjects (men: δ=15.1 nmol/l, P<0.001; women: δ=72.9 nmol/l, P<0.001) independent of age, BMI and fasting glucose levels. Conclusion These findings are consistent with high levels of SHBG in T1D, and correspondingly low levels in T2D subjects, suggesting an inhibitory effect of insulin on the SHBG production in the liver.

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Metformin Inhibits N-Methyl-N-Nitrosourea Induced Gastric Tumorigenesis in db/db Mice

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0043-100118 ◽

2017 ◽

Vol 125 (06) ◽

pp. 392-399 ◽

Cited By ~ 3

Author(s):

Shan Zhuang ◽

Yongmei Jian ◽

Yongning Sun

Keyword(s):

Gastric Cancer ◽

Type 2 Diabetes ◽

Inflammatory Cytokines ◽

Serum Insulin ◽

Inhibitory Effect ◽

Increased Risk ◽

Pro Inflammatory Cytokines

Abstract Type 2 diabetes can elevate risk of gastric cancer and metformin, an anti-diabetic agent, has an inhibitory effect against gastric cancer cell in vitro. However, the effect of metformin on type 2 diabetes-related gastric tumorigenesis in vivo is still not clear. In the present study, we aim to detect whether metformin can inhibit increased risk of gastric cancer in diabetic db/db mice and which the potential anti-cancer mechanisms of metformin are. 4-week-old mice were divided into 3 groups (2 db/db mice groups and one wild type mice group). All diabetic and non-diabetic mice were treated with N-Methyl-N-Nitrosourea (MNU) for 20 weeks to induce gastric tumorigenesis. At week 21, one db/db mice group were treated with metformin (5 mg/ml) for 10 weeks and the other 2 groups were treated with saline. Blood samples were collected for testing insulin and insulin-like growth factor (IGF)-1. Stomach tissues were collected for histopathological evaluation and mRNAs analysis. Metformin significantly decreased incidence of MNU-induced gastric dysplasia and cancer in diabetic db/db mice. Furthermore, metformin reduced serum insulin as well as IGF-1, and also suppressed expression of insulin receptor, IGF-1, IGF-1 receptor and several pro-inflammatory cytokines mRNAs in stomach of db/db mice, but did not significantly influence IGF-2 and IGF-2 receptor expressions. The results show that metformin can prevent the risk of gastric cancer in type 2 diabetes and the protective mechanisms may involve in an inhibitory effect of metformin on insulin as well as IGF-1 signals and cancer related pro-inflammatory cytokines.

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Exocrine Pancreatic Function in Girls with Anorexia Nervosa

Nutrients ◽

10.3390/nu13093280 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3280

Author(s):

Żaneta Malczyk ◽

Wojciech Roczniak ◽

Bogdan Mazur ◽

Jarosław Kwiecień ◽

Katarzyna Ziora ◽

...

Keyword(s):

Anorexia Nervosa ◽

Leptin Receptor ◽

Serum Insulin ◽

Study Groups ◽

Exocrine Pancreatic Function ◽

Exocrine Function ◽

Time To Peak ◽

Soluble Leptin Receptor ◽

Pancreatic Exocrine ◽

The Relationship

Objectives: To assess pancreatic exocrine function in patients with anorexia nervosa using a breath test with 13C-labeled mixed triglycerides (MTG-BT) and to determine the relationship between the test results and selected biochemical and hormonal parameters. Material and methods: Anthropometric measurements, biochemical and hormonal parameters (serum leptin, soluble leptin receptor (sLR), acylated and desacylated ghrelin, free leptin index (FLI)), and MTG-BT were performed in a group of 31 girls with the restrictive type of AN, as well as 38 healthy girls (C). Results: The average cumulative dose of 13C-triglycerides recovered with exhaled air (%CD) was similar in both study groups, while the average time from 13C-triglycerides administration to peak 13CO2 excretion in expired air (time to peak (TTP)) was significantly longer in patients with AN compared to C. In both groups, %CD correlated negatively with FLI. TTP correlated negatively with sLR and FLI in the AN and with serum insulin and HOMA-IR values in the C. Conclusions: In girls with AN, the pancreatic efficiency of lipase secretion was found to be normal, while the kinetics of this enzyme secretion were disturbed. These changes may result from disorders in the functioning of the adipose–insular and islet–acinar axes.

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