Effects of exendin-4 and selenium on the expression of GLP-1R, IRS-1, and preproinsulin in the pancreas of diabetic rats.

The mechanisms by which exendin-4 and selenium exert their antidiabetic actions are still unclear. Here, we investigated the effects of exendin-4 or selenium administration on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and preproinsulin in the pancreas of diabetic rats. Diabetes was induced by streptozotocin administration.

Effects of selenium and exendin-4 on glucagon-like peptide-1 receptor, IRS-1, and Raf-1 in the liver of diabetic rats.

Selenium and exendin-4 exert antidiabetic effects by unknown mechanisms. Herein, we investigated their effects on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and Raf-1 in the livers of rats with streptozotocin-induced diabetes. Diabetic rats were injected intraperitoneally with exendin-4 (0.

Role of glucagon-like peptide-1 and its agonists on early prevention of cardiac remodeling in type 1 diabetic rat hearts.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from intestinal L cells upon nutrients ingestion, and is currently used for treating diabetes mellitus. It plays an important role in receptor modulation and cross talk with insulin at the coronary endothelium (CE) and cardiomyocytes (CM) in diabetic type 1 rat heart model. We studied the effects of insulin, GLP-1 analogues (exendin-4), and dipeptidyl peptidase-IV (DPP-IV) inhibitor on GLP-1 cardiac receptor modulation.

Role of insulin on jejunal PepT1 expression and function regulation in diabetic male and female rats.

The aim of this study was to determine whether the jejunal oligopeptide transporter PepT1 is regulated by insulin and whether this regulation is sex-dependent in type 1 diabetic rats. PepT1 expression, real-time polymerase chain reaction, and Western blots were performed using jejunal segments from 4 groups of male and female rats: normal (nondiabetic), insulin-treated nondiabetic, streptozotocin (STZ)-induced diabetic (type 1 diabetes), and insulin-treated diabetic models. Furthermore, the same segments from all groups underwent perfusion to assess uptake of the dipeptide glycylsarcosine through PepT1.

Role of glucagon-like peptide-1 analogues on insulin receptor regulation in diabetic rat hearts.

This study focused on the regulation and affinity modulation of the insulin receptor of coronary endothelium and cardiomyocytes in nondiabetic and STZ-induced type 1 diabetic rats. Male rats were divided into the following 9 groups: nondiabetic (N), nondiabetic treated with exendin-4 (NE), nondiabetic treated with dipeptidyl peptidase IV (DPP-IV) inhibitor (NDp), diabetic (D), diabetic treated with insulin (DI), diabetic treated with exendin-4 (DE), diabetic co-treated with insulin and exendin-4 (DIE), diabetic treated with DPP-IV inhibitor (DDp), and diabetic co-treated with insulin and DPP-IV inhibitor (DIDp). After the rats were treated for 1 month, a first-order Bessel function was employed to estimate the insulin binding affinity (with time constant tau = 1/k-n) to its receptors on the coronary endothelium and cardiomyocytes using CHAPS-untreated and CHAPS-treated heart perfusion, respectively.

Cross-talk related to insulin and angiotensin II binding on myocardial remodelling in diabetic rat hearts.

This study focused on the regulation and affinity modulation of angiotensin II (Ang II) binding to its receptor subtypes (AT(1)- and AT(2)-receptor) in the coronary endothelium (CE) and cardiomyocytes (CM) of Sprague-Dawley male rats in normal (N), normal treated with losartan (NL), streptozotocin-induced diabetic (D), insulin-treated diabetic (DI), losartan-treated diabetic (DL), and diabetic co-treated with insulin and losartan (DIL). Heart perfusion was used to estimate Ang II binding affinity (tau=1/k-(n)) to its receptor subtypes on CE and CM. Diabetes decreased tau value on CE and increased it on CM as compared to normal.

Effect of type-1 diabetes mellitus on the regulation of insulin and endothelin-1 receptors in rat hearts.

This project assesses the treatment role with insulin and (or) angiotensin II receptor subtype-1 (AT1-R) blocker (ARB) on insulin receptor and endothelin-1 receptor subtype (ETA-R and ETB-R) regulation in rat hearts suffering from insulin-dependent diabetes mellitus (IDDM). Animals were divided into 6 groups: groups 1, 3, and 5 were controls consisting of normal, diabetic (streptozotocin-treated, once at 0 time), and diabetic supplemented daily with insulin, respectively, whereas groups 2, 4, and 6 were the controls treated daily with losartan. One month after enrollment, rats were sacrificed and samples of cardiac tissue were snapped frozen for immunostaining and Western blotting.

Effect of systemic insulin and angiotensin II receptor subtype-1 antagonist on endothelin-1 receptor subtype(s) regulation and binding in diabetic rat heart.

This study reports on the regulation and remodeling role of endothelin-1 (ET-1) and its receptor subtypes, ET(A)-Rs/ET(B)-Rs, at the coronary endothelium (CE) and cardiomyocyte (CM) sites. It is carried out in normal and normotensive rats with streptozotocin-induced diabetes mellitus receiving different treatment modalities. Normal rats were divided into two groups, namely a placebo (N) and a losartan-treated (NL), and diabetic rats into four groups receiving placebo (D), insulin-treated (DI), losartan-treated (DL), and insulin/losartan-treated (DIL) respectively.

Comparative pharmacokinetics and metabolic pathway of gemcitabine during intravenous and intra-arterial delivery in unresectable pancreatic cancer patients.

Background: To study the pharmacokinetics and clinical outcome of gemcitabine (2'-2'-difluoro-deoxcytidine [dFdC]) during intra-arterial versus intravenous delivery in locally advanced and regionally metastatic pancreatic cancer.

Patients And Methods: Seven patients with unresectable pancreatic cancer received escalating intra-arterial doses of gemcitabine ranging from 800 to 1400 mg/m2, after selective embolisation of all pancreatic blood supply, except for the tumour-feeding arteries. Four patients received intravenous gemcitabine (control).

Effect of diabetes mellitus and insulin on the regulation of the PepT 1 symporter in rat jejunum.

This investigation focused on studying the effects of insulin-dependent diabetes mellitus and insulin treatment on absorption of glycylsarcosine (Gly-Sar) across the Sprague-Dawley rat jejunum, using in situ perfusion in a physiologic acidic microenvironment at pH 6.0. Rats were divided into five groups: normal controls in group I, normal colchicine-treated rats in group II, normal cytochalasin-treated rats in group III, streptozotocin-induced diabetic rats in group IV, and insulin-treated diabetic rats in group V.

Effect of insulin and angiotensin II receptor subtype-1 antagonist on myocardial remodelling in rats with insulin-dependent diabetes mellitus.

Objectives: To assess the role of insulin or an angiotensin II receptor antagonist (losartan), or both, in preventing cardiomyocyte damage in rats suffering from insulin-dependent diabetes mellitus (IDDM), and to correlate it with insulin receptor modulation at the cardiomyocyte, coronary endothelium and skeletal muscle cell level.

Design: Animals were divided into groups of normal rats, diabetic rats, and diabetic rats given insulin, each subdivided into a control group and an experimental group treated with losartan.

Methods: The animals were killed 1 month after enrollment to the study.

Endothelium and myocyte cellular insulin receptor alterations in a rat model of myocardial infarction.

Ischemic heart disease is considered to be one of the leading causes of death in adults. While extensive research on mechanisms contributing to the pathogenesis of myocardial infarction (MI) has been underway, it is not known whether insulin receptor characteristics and postreceptor signaling have been fully addressed as yet. Present work attempts to investigate whether the remodeling process effectively induces alteration(s) in insulin-binding characteristics at the coronary endothelium and cardiomyocytes using a rat heart model of MI.

Regulation of insulin-like growth factor-1 by the renin-angiotensin system during regression of cardiac eccentric hypertrophy through angiotensin-converting enzyme inhibitor and AT1 antagonist.

Angiotensin II (Ang II) mediates its effects through its non-tyrosine-kinase G protein coupled Ang-II type 1 receptor (AT1). Growing evidence indicates that a functional insulin-like growth factor-1 (IGF-1) tyrosine kinase receptor is required for Ang-II-induced mitogenesis. Along with Ang II, we have previously shown that changes in IGF-1 receptor binding at myofibers are causative agents for cardiac eccentric hypertrophy.

Endothelin-1 receptor subtypes expression and binding in a perfused rat model of myocardial infarction.

Endothelin-1 (ET-1) pathophysiologic actions are mediated via binding with two receptor subtypes, ET(A) and ET(B). Release of ET-1 from endocardial endothelial cells and cardiac myocytes can modulate heart tissue necrosis and alterations. This study investigates the remodeling processes in Sprague-Dawley rats of myocardial infarction (MI) induced by ligating the left anterior descending coronary artery.

Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarction.

Clinical evidence points to a role for angiotensin II (Ang II) in the post-infarction remodelling of cardiac hypertrophy. The present study was designed to investigate the remodelling process in an animal model of myocardial infarction (MI) using the following criteria: 1) histological studies to examine the re-vascularisation process and collagen deposition in different regions of the myocardium; 2) histological evidence to investigate the cell type distribution using cell-specific markers; 3) histological and Western blot analysis to localise Ang II receptor subtypes (AT(1)-receptor and AT(2)-receptor) and to study their regulation; 4) kinetics of the binding of Ang II to its receptors in a heart perfusion model; and 5) to assess the effect of the Ang II antagonist (losartan) on these parameters. MI was induced by ligation of the left anterior descending coronary artery of Sprague-Dawley rats.

Kinetics of lipopolysaccharide clearance by Kupffer and parenchyma cells in perfused rat liver.

We studied the kinetics of [3H]lipopolysaccharide ([3H]LPS) (endotoxin) binding to Kupffer cells and hepatocytes at the level of the microtubular system after treatment with gadolinium chloride (GdCl(3)) and colchicine. Liver perfusion in Sprague-Dawley rats involves both portal vein and thoracic inferior vena cava cannulations as inlet and outlet, respectively. The subhepatic inferior vena cava is ligated to prevent perfusate leakage.

Characterization of insulin-resistance: role of receptor alteration in insulin-dependent diabetes mellitus, essential hypertension and cardiac hypertrophy.

Insulin-resistance is associated with a number of disease states such as diabetes, syndrome X, and hypertension. These situations may be coupled to insulin-resistance through the insulin signaling system as a common pathway. The purpose of this study was to investigate the receptor binding alterations in streptozotocin-induced diabetic rats, spontaneously hypertensive rats and aortocaval shunted rats (eccentric cardiac hypertrophy).

Two uncompetitive, activated, and transport sites of the Na+/H+ exchanger for pH regulation in perfused rat kidney.

The purpose of this study is to assess the effect of an apparent alteration in intracellular pH and the effect of amiloride on the activity of the Na+/H+ antiporter in perfused rat kidney. Rat kidney-Na+ retention was determined using tracer 22Na in perfusate composed of HCl-glycine buffer (pH 3.80 to pH 5.

Insulin-receptor binding characteristics in perfused SHR and WKY rat hearts.

This work uses a new heart-perfusion technique to measure 125I-insulin binding on capillary endothelium and myofiber cell membranes in Wistar-Kyoto and spontaneously hypertensive rats. Ringer-Lock buffer was infused at a rate of 1 ml min-1 in the presence of 20 meq l-1 K+ and 125I-insulin through an aortic cannula. The effluent was collected through a catheter introduced into the right atrium.

Angiotensin II delivery and binding at the microvascular endothelium and cardiac myocyte surfaces in perfused rat hearts.

Peptide delivery toward its targets in an intact organ is equally as important as its routing from the systemic circulation to cell surface receptor sites. A physical model pertinent to a heart perfusion technique in Sprague-Dawley rats is presented describing reversible binding of angiotensin II and/or antagonist (DUP 753, losartan) with the microvascular endothelial receptor subtypes as well as with the cardiac myocyte receptor subtypes that are exposed to the perfusate by CHAPS-treatment. Analysis of the collected effluents are curve-fitted with a conservation equation and a first-order Bessel function.

Binding of 125I-insulin on capillary endothelial and myofiber cell membranes in normal and streptozotocin-induced diabetic perfused rat hearts.

A heart-perfusion technique was employed to measure 125I-insulin binding on capillary endothelial and myocyte cell membranes in Sprague-Dawley rats. Animals were anesthetized, and the anterior chest wall excised to expose the mediastinal contents. The right and left superior and inferior venae cavae were dissected and tied, and another tie was passed around the aorta.