scholarly journals Endothelial dysfunction precedes hypertension in diet-induced insulin resistance

1998 ◽  
Vol 275 (3) ◽  
pp. R788-R792 ◽  
Author(s):  
Prasad V. G. Katakam ◽  
Michael R. Ujhelyi ◽  
Margarethe E. Hoenig ◽  
Allison Winecoff Miller

The insulin-resistant (IR) syndrome may be an impetus for the development of hypertension (HTN). Unfortunately, the mechanism by which this could occur is unclear. Our laboratory and others have described impaired endothelium-mediated relaxation in IR, mildly hypertensive rats. The purpose of the current study is to determine if HTN is most likely a cause or result of impaired endothelial function. Sprague-Dawley rats were randomized to receive a fructose-rich diet for 3, 7, 10, 14, 18, or 28 days or were placed in a control group. The control group received rat chow. After diet treatment, animals were instrumented with arterial cannulas, and while awake and unrestrained, their blood pressure (BP) was measured. Subsequently, endothelium-mediated relaxation to acetylcholine was determined (in vitro) by measuring intraluminal diameter of phenylephrine-preconstricted mesenteric arteries (∼250 μM). Serum insulin levels were significantly elevated in all groups receiving fructose feeding compared with control, whereas there were no differences in serum glucose levels between groups. Impairment of endothelium-mediated relaxation starts by day 14 [mean percent maximal relaxation (Emax): 69 ± 10% of baseline] and becomes significant by day 18 (Emax: 52 ± 11% of baseline; P < 0.01). However, the mean BP (mmHg) does not become significantly elevated until day 28 [BP: 132 ± 1 ( day 28) vs. 116 ± 3 (control); P < 0.05]. These findings demonstrate that both IR and endothelial dysfunction occur before HTN in this model and suggest that endothelial dysfunction may be a mechanism linking insulin resistance and essential HTN.

Author(s):  
Narendar Koyagura ◽  
I M Nagendra Nayak ◽  
M G Jamadar ◽  
Ashok M Patil ◽  
Sanjit Anand

<p>ABSTRACT<br />Objective: This study was undertaken to evaluate the preventive effect of heartwood of P. marsupium in dexamethasone-induced hyperinsulinemia<br />and hyperglycemia and compare it with that of pioglitazone.<br />Methods: Male albino wistar rats were divided into five groups (n=6). Plain control group received gum acacia (2%) orally from d 1 to d 12. Dexa<br />control group received gum acacia (2%) orally for d 1 to d 12 and Dexa (8 mg/kg) intraperitoneal (i.p.) from d 7 to d 12, during the study period.<br />Two test groups received ethanolic extract of Pterocarpus marsupium heartwood (PME) (1 and 2 g/kg/) per oral (PO), and standard control group<br />received pioglitazone (60 mg/kg/PO) from d 1 to d 12. During the 12-d study period, the two test groups and standard control group received Dexa<br />(8 mg/kg/i.p.) from d 7 to d 12. On last day of the study, the blood samples were collected by retro-orbital sinus punctureand used for estimation of<br />serum insulin and glucose levels. Homeostatic Model Assessment (HOMA) method was employed to calculate the degree of insulin resistance(IR).<br />Results were analyzed by using one-way analysis of variance followed by Scheffe’s multiple comparison test (p&lt;0.05).<br />Results: Treatment with ethanolic extract of P. marsupium and pioglitazone significantly (p&lt;0.05) reduced the elevated insulin and glucose levels as<br />well as HOMA-IR and HOMA-IS values in dexa treated animals.<br />Conclusion: Ethanolic extract of P. marsupium heartwood effectively countered dexamethasone-induced hyperinsulinemia and hyperglycemia.<br />Insulin-sensitizing activity of P. marsupium heartwood was found to be more effective than pioglitazone.<br />Keywords: Pterocarpus marsupium, Insulin resistance, Hyperinsulinemia, Hyperglycemia.</p>


1991 ◽  
Vol 261 (6) ◽  
pp. E692-E697 ◽  
Author(s):  
T. A. Kotchen ◽  
H. Y. Zhang ◽  
M. Covelli ◽  
N. Blehschmidt

In normal rats, sucrose feeding results in insulin resistance and an elevation of arterial pressure. The purpose of this study was twofold: 1) to evaluate the effect of sucrose feeding on blood pressure in a genetic model and in an acquired model of hypertension and 2) to determine whether these models of hypertension are associated with insulin resistance. In Dahl salt-resistant (Dahl-R) rats on both a 0.45 and a 3% NaCl intake, systolic blood pressures were higher (P less than 0.01) in sucrose-drinking than in water-drinking animals. In contrast, blood pressure was not affected by dietary sucrose in Dahl salt-sensitive (Dahl-S) rats. Blood pressure was also not affected by sucrose in the one-kidney, one-clip (1K,1C) hypertensive rat. In response to an oral glucose load, serum glucose was similar in Dahl-R and Dahl-S rats, although serum insulin was higher (P less than 0.05) in Dahl-S rats, suggesting that Dahl-S rats are insulin resistant. In contrast, glucose and insulin responses were similar in hypertensive 1K,1C animals and normotensive controls. In conclusion, sucrose feeding increased blood pressure in Dahl-R but not in Dahl-S or 1K,1C hypertensive rats. Additionally, Dahl-S rats, but not hypertensive 1K,1C rats, are insulin resistant.


Author(s):  
Samruddhi Kavishwar ◽  
Mrinal Sanaye ◽  
Monisha Nair ◽  
Mukesh Chawda ◽  
Viplav Kshirsagar ◽  
...  

Abstract Objectives Madhumeha Kusumakar Rasa (MKR) is an Ayurved formulation having a strong pharmacological base for diabetes management. This study aimed to validate MKR's efficacy in dexamethasone-induced insulin resistance (IR). Methods Albino Wistar rats were divided into four groups. Group 1 served as the normal control, Group 2 received dexamethasone 1.5 mg/kg (i.p.), Group 3 received dexamethasone and metformin 200 mg/kg (p.o.), and Group 4 received dexamethasone and MKR 236 mg/kg (p.o.). Animals were evaluated for serum glucose levels and glucose tolerance, serum insulin, Homeostatic model assessment of insulin resistance (HOMA-IR), Homeostatic model assessment of insulin sensitivity (HOMA-IS), fasting glucose to insulin ratio (FGIR), and lipid parameters. Pancreas, liver, and kidneys were evaluated for reduced Glutathione (GSH) and Malondialdehyde (MDA) levels. These tissues were also evaluated for histopathological changes. Results MKR showed significant improvement in serum glucose and glucose tolerance, serum insulin and HOMA-IR, HOMA-IS, and FGIR. It also showed a significant improvement in lipid parameters as compared to the dexamethasone-treated group. It prevented depletion of GSH levels and elevation in MDA levels. These effects were supported by histopathological analysis. Conclusions MKR treatment significantly attenuated dexamethasone-induced IR. This study validates the mechanism of the anti-diabetic potential of MKR.


2020 ◽  
Vol 27 (07) ◽  
pp. 1396-1400
Author(s):  
Sidra Arshad ◽  
Muhammad Sajid Mehmood ◽  
Lubna Siddique ◽  
Shahida Parveen ◽  
Amina Rasul ◽  
...  

A number of endocrine hormones play a significant role in glycemic control of the body. Insulin and glucagon are two contrasting hormones which work in close association to maintain a normal fuel balance. Thyroid hormones also have a key role in regulating blood glucose levels. Several studies have suggested that type 2 diabetes mellitus (T2DM) have increased incidence of thyroid abnormalities. Objectives: To determine correlation between insulin to glucagon ratio and thyroid hormones levels in the two groups. Study Design: Randomized Control Trial. Settings: Physiology Department of Army Medical College, Rawalpindi and National Institute of Health (NIH), Islamabad. Period: 6 months (from 1st January 2017 to 30th June 2017). Material & Methods: A sample of sixty apparently healthy Sprague Dawley rats was selected randomly. It was divided into two groups i.e control and diabetic. It was ensured that all the rats were euglycemic and euthyroid at the start of the study by investigating serum thyroid stimulating hormone (TSH) and serum glucose levels. The control group was given with normal pellet diet whereas, STZ induced rats were fed on high fat diet while. The control group were injected with saline injection intraperitoneally after 2 weeks, while low dose of streptozotocin was injected to diabetic rats. The induction of diabetes mellitus was affirmed by checking plasma glucose levels and homeostatic model for insulin resistance (HOMA-IR). The specific diet was continued for another five weeks in both the groups. The terminal sample was investigated for plasma glucose using glucose oxidase method and serum insulin, TSH, T3 and T4 levels using ELISA technique. Results: The serum insulin and glucose levels were elevated in diabetic group as compared to the control group. HOMA-IR was also raised significantly in the diabetic group. The serum TSH and T4 levels were considerably higher (p˂0.001) while serum T3 was comparable in both the groups. There was no correlation between Insulin to Glucagon Ratio and TSH, T3 and T4 both in control and diabetic groups. Conclusion: Serum glucose, serum insulin and HOMA-IR were raised in the diabetic group. Serum TSH and T4 levels were also increased while no change in serum T3 levels. IGR and thyroid hormones were not correlated in either group.


2007 ◽  
Vol 35 (06) ◽  
pp. 1037-1046 ◽  
Author(s):  
Yolanda Y. Pérez ◽  
Enrique Jiménez-Ferrer ◽  
Alejandro Zamilpa ◽  
Marcelino Hernández-Valencia ◽  
Francisco J. Alarcón-Aguilar ◽  
...  

Insulin resistance, which precedes type 2 diabetes mellitus (T2DM), is a widespread pathology associated with the metabolic syndrome, myocardial ischemia, and hypertension. Finding an adequate treatment for this pathology is an important goal in medicine. The purpose of the present research was to investigate the effect of an extract from Aloe vera gel containing a high concentration of polyphenols on experimentally induced insulin resistance in mice. A polyphenol-rich Aloe vera extract (350 mg/kg) with known concentrations of aloin (181.7 mg/g) and aloe-emodin (3.6 mg/g) was administered orally for a period of 4 weeks to insulin resistant ICR mice. Pioglitazone (50 mg/kg) and bi-distilled water were used as positive and negative controls respectively. Body weight, food intake, and plasma concentrations of insulin and glucose were measured and insulin tolerance tests were performed. The insulin resistance value was calculated using the homeostasis model assessment for insulin resistance (HOMA-IR) formula. Results showed that the polyphenol-rich extract from Aloe vera was able to decrease significantly both body weight ( p < 0.008) and blood glucose levels ( p < 0.005) and to protect animals against unfavorable results on HOMA-IR, which was observed in the negative control group. The highest glucose levels during the insulin tolerance curve test were in the negative control group when compared to the Aloe vera extract and pioglitazone treated mice ( p < 0.05). In conclusion, Aloe vera gel could be effective for the control of insulin resistance.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ann-Yae Na ◽  
Jung Jae Jo ◽  
Oh Kwang Kwon ◽  
Piljoung Cho ◽  
Yan Gao ◽  
...  

AbstractGinseng (Panax ginseng Meyer) is commonly used as an herbal remedy worldwide. Few studies have explored the possible physiological changes in the liver although patients often self-medicate with ginseng preparations, which may lead to exceeding the recommended dose for long-term administration. Here, we analyzed changes in the hepatic proteins of mouse livers using quantitative proteomics after sub-chronic administration of Korean red ginseng (KRG) extract (control group and 0.5, 1.0, and 2.0 g/kg KRG) using tandem mass tag (TMT) 6‐plex technology. The 1.0 and 2.0 g/kg KRG groups exhibited signs of liver injury, including increased levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) in the serum. Furthermore, serum glucose levels were significantly higher following KRG administration compared with the control group. Based on the upregulated proteins found in the proteomic analysis, we found that increased cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) levels promoted greater hydrogen sulfide (H2S) synthesis in the liver. This investigation provides novel evidence that sub-chronic administration of KRG can elevate H2S production by increasing protein expression of CBS and CSE in the liver.


2021 ◽  
Vol 11 (9) ◽  
pp. 1812-1817
Author(s):  
Jingjing Zhou ◽  
Wenjuan Zhu ◽  
Zheng Mao ◽  
Zhen Li ◽  
Xiaoqin Li ◽  
...  

Background: The objective of the research was to investigate the roles of miR-4458 in the regulation of insulin resistance in hepatic cells and to explore the underlying molecular mechanisms. Methods: The blood samples were collected from the T2D patients and the health controls, and the liver tissues were collected from the DM and control rats. The relationship between IGF1R and miR-4458 was predicted by TargetScan and verified by the dual luciferase reporter gene system. qRT-PCR was used to measure the mRNA expression of miR-4458, IGF1R, G6Pase and PEPCK. The protein expression of IGF1R, p-AKT and AKT were measured by Western blot analysis. The rat insulin ELISA Kit and glucose Uptake Colorimteric Assay Kit were used to determine the level of serum insulin and the glucose uptake. Results: miR-4458 was high expressed in T2D patients. We predicted and verified that IGF1R was a direct target of miR-4458, and the mRNA expression of IGF1R was reduced in type 2 diabetes patients. We established the diabetes model (DM) and IR HepG2 cell model, and found that the blood glucose and serum insulin levels were significantly elevated in the DM group. miR-4458 expression was up-regulated, while the expression of IGF1R and p-AKT, and p-AKT/AKT ratio were reduced in the DM group and IR HepG2 cell model. miR-4458 inhibitor and IGF1R-siRNA significantly decreased the expression of miR-4458 and IGF1R respectively. In comparison with IR+inhibitor control group, miR-4458 inhibitor increased 2-DG6P content, IGF1R expression, p-AKT expression and p-AKT/AKT ratio, reduced the expression of G6Pase and PEPCK, and all the effects were reversed by down-regulating IGF1R. Conclusion: miR-4458 regulated the insulin resistance in hepatic cells by regulating the IGF1R/PI3K/AKT signal pathway, which will be a potential target for the treatment of diabetes.


1989 ◽  
Vol 256 (2) ◽  
pp. E231-E235
Author(s):  
G. A. Smythe ◽  
W. S. Pascoe ◽  
L. H. Storlien

Central noradrenergic pathways play a significant role in mediating blood glucose levels after neuroglycopenia. To further investigate hypothalamic noradrenergic neuronal activity (NNA) and sympathoadrenal influences in glucoregulation, we studied the effects of acute stress on glycemia and insulin release in normal and adrenalectomized (ADRX) rats. Within 5 min of exposure of rats to ether or cold-swim stress, significant positive correlations were evident between hypothalamic NNA and serum glucose levels (r = 0.70, P less than 0.001; at 15 min r = 0.78, P less than 0.0001). Five minutes after stress in the intact rat, insulin release was inhibited and serum insulin levels inversely correlated to hypothalamic NNA (r = 0.45, P less than 0.05). This relationship between insulin and NNA was no longer present 15 min after stress, but the levels of insulin remained inappropriately low with respect to the elevated serum glucose levels (approximately 30% above basal). Blockade of sympathetic noradrenergic pathways by treatment of intact rats with guanethidine prevented the rise in glucose after cold-swim stress but did not prevent the inhibition of insulin release. Fifteen minutes after exposure of ADRX rats to cold-swim stress their hypothalamic NNA and serum glucose levels were similar to intact animals. However, in contrast to their intact counterparts, serum insulin levels were significantly elevated (P less than 0.01). These data are consistent with central noradrenergic neural pathways directly mediating hepatic glucose release and indirectly inhibiting pancreatic insulin release via activation of adrenal medullary catecholamines.


2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Eun Yeong Jang ◽  
Yejin Ahn ◽  
Hyung Joo Suh ◽  
Ki-Bae Hong ◽  
Kyungae Jo

Constipation is a chronic disease caused by infrequent, inadequate, and difficult bowel movements. The present study aimed to evaluate the potential laxative effect of maltooligosaccharide (MOS) on loperamide-induced constipation in a rat model. In vitro experiments were conducted to evaluate the effect of MOS on the growth of lactic acid bacteria. Moreover, to examine the effect of MOS administration on Sprague-Dawley (SD) rats with loperamide-induced constipation, the drinking water for the rats was supplemented with 10% or 15% of MOS for 14 days, and, thereafter, the improvement in constipation was assessed. For this, the rats were divided into five groups: normal (Nor), loperamide-induced constipated (Con), positive control (15% of dual-oligosaccharide (DuO-15)), 10% MOS treated (MOS-10), and 15% MOS-treated (MOS-15). In an in vitro test, MOS treatment promoted the growth of lactic acid bacteria except Lactobacillus bulgaricus. Treatment with higher MOS dose relieved constipation in rats by improving the fecal pellet and water content. Furthermore, in the high MOS dose group, the cecal short-chain fatty acid levels significantly increased compared to those in the control group (P<0.001). MOS treatment also improved the mucosal thickness as well as mucin secretion and increased the area of intestinal Cajal cells compared to that in the control group (P<0.001). These findings suggest that MOS relieves constipation and has beneficial effect on the gastrointestinal tract, and, therefore, it can be used as an ingredient in functional foods for treating constipation or improving intestinal health.


2015 ◽  
Vol 7 (2) ◽  
pp. 41-46
Author(s):  
S Sultana ◽  
Z Zeba ◽  
A Hossain ◽  
A Khaleque ◽  
R Zinnat ◽  
...  

Hyperproinsulinemia is commonly present in subjects with impaired glucose tolerance. The present study was undertaken to investigate the proinsulin level in Bangladeshi IGT subjects and to explore its association with insulin resistance. This observational study was conducted under a case-control design with IGT subjects (n=50) and controls (n=44). IGT was diagnosed following the WHO Study Group Criteria. Serum glucose was measured by glucose-oxidase method, serum lipid profile by enzymatic method and serum insulin and serum proinsulin were measured by ELISA method. Insulin secretory capacity (HOMA%B) and insulin sensitivity (HOMA%S) were calculated from fasting serum glucose and fasting serum insulin by homeostasis model assessment. The study subjects were age- and BMI- matched. Mean (±SD) age (yrs) of the control and IGT subjects were 40±6 and 40±5 respectively (p=0.853). Mean (±SD) BMI of the control and IGT subjects were 23±3 and 22±2 respectively (p=0.123). Fasting glucose was not significantly higher in IGT subjects, but serum glucose 2 hours after 75 gm glucose load was significantly higher in IGT subjects. Median (Range) value of fasting serum glucose (mmol/l) of control and IGT subjects were 5.3 (3.8-6) and 5.2 (4-12) respectively; (p=0.297). Median (Range) value of serum glucose (mmol/l) 2 hours after 75 gm glucose load of control and IGT subjects were 6.1 (3-7.8) and 7.9 (5- 21) respectively; (p=0.001). Fasting TG was significantly higher in IGT subjects and LDL-c was significantly lower in IGT subjects. Serum Total cholesterol and HDL-c were not significantly different between the IGT and control subjects. Median (Range) value of fasting serum TG (mg/dl) of control and IGT subjects were 119 (51-474) and 178 (82-540) respectively; (p=0.001). Median (Range) value of fasting serum T chol (mg/dl) of control and IGT subjects were 180 (65-272) and 186 (140-400) respectively; (p=0.191). Median (Range) value of fasting serum HDL-C (mg/dl) of control and IGT subjects were 29 (19-45) and 31 (15-78) respectively; (p=0.914). Median (Range) value of fasting serum LDL-C (mg/dl) of control and IGT subjects were 117(29-201) and 111(41- 320) respectively; (p=0.001). Fasting serum proinsulin was significantly higher in IGT subjects. Median (Range) value of fasting serum proinsulin (pmol/l) of control and IGT subjects were 9.2(1.8-156) and 17(3-51) respectively; (p=0.001). Insulin secretory capacity (HOMA%B) was higher but insulin sensitivity (HOMA%S) was significantly lower in case of IGT subjects. Median (Range) value of HOMA%B of control and IGT subjects were 97(46-498) and 164(17-300) respectively; (p=0.001). Median (Range) value of HOMA%S of control and IGT subjects were 68(19-270) and 39(15-110) respectively (p=0.001). In multiple regression analysis a significant negative association was found between fasting proinsulin and insulin sensitivity (p=0.037). The data led to the following conclusions: a) Insulin resistance is the predominant defect in Bangladeshi IGT subjects. b) Basal proinsulin level is significantly increased in IGT subjects. c) Insulin resistance is negatively associated with serum proinsulin in IGT subjects. DOI: http://dx.doi.org/10.3329/bjmb.v7i2.22411 Bangladesh J Med Biochem 2014; 7(2): 41-46


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