In this study we evaluated whether the activation of endogenous angiotensin-converting enzyme (ACE) 2 would improve the cardiovascular autonomic dysfunction of diabetic rats. Ten days after type 1 diabetes induction (Streptozotocin, STZ, 50mg/kg i.v.), the rats were orally treated with 1-[(2-dimethylamino)ethylamino]-4-(hydroxymethyl)-7-[(4-methylphenyl) sulfonyl oxy]-9H-xanthene-9-one (XNT), a newly discovered ACE2 activator (1mg/kg/day), ...

OBJECTIVE: Patients with liver cirrhosis suffer from hyperinsulinemia, hyperglucagonemia and a certain degree of insulin resistance, and portosystemic shunts may be involved in the etiology. A transjugular intrahepatic portosystemic shunt (TIPS) as a treatment for the complications of portal hypertension leads to hemodynamic changes. The objective of the present study ...

BACKGROUND & AIMS: Cirrhosis of the liver is characterised by insulin resistance and low levels of insulin-like growth factor I (IGF-I). Lack of IGF-I may contribute to this insulin resistance, as IGF-I increases insulin sensitivity. This study aimed to determine the effects of normalisation of IGF-I on insulin action in ...

Decreased glucose tolerance and diabetes are frequently observed in advanced liver cirrhosis patients and may be related to insulin resistance. Glucose transporter-4 (GLUT4), one of the most important glucose transporters, plays a key role in the development of type 2 diabetes. In order to study the mechanism of insulin resistance ...

Disturbance of glucose metabolism is a common feature in liver cirrhosis which is associated with insulin resistance and is an established risk factor for disease progression and survival in patients with chronic liver diseases. We investigated whether umbilical cord blood-derived mesenchymal stem cells (HMSCs) have an effect on the expression ...

BACKGROUND: Up to 30% of the cirrhotic patients may clinically be classified as having diabetes. The aims of this retrospective study were to evaluate the prevalence of diabetes, its association with the severity of cirrhosis, and subsequent implication on mortality in a broad population of cirrhotic patients in Taiwan. METHODS: ...

Nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase complex has been shown to be involved in the process of glucose-stimulated insulin secretion (GSIS). In this study, we examined the effect of palmitic acid on superoxide production and insulin secretion by rat pancreatic islets and the mechanism involved. Rat pancreatic islets were incubated ...

BACKGROUND: In liver cirrhosis an abnormal glucose tolerance correlates with a poor long-term prognosis. The aim of this study was to evaluate whether a disturbed glucose metabolism predicts the short-term prognosis in hospitalized patients with decompensated liver cirrhosis. METHODS: Seventy-eight patients with liver cirrhosis were prospectively enrolled. Disturbed glucose metabolism ...

Insulin/alginate (ALG) microcapsules for controllable release and side effect reduction of a glucocorticoid have been fabricated via the layer-by-layer (LbL) assembly technique. Insulin and ALG are deposited alternately onto hydrocortisone (HC) crystals to form a core-shell structure. This insulin/ALG microcapsule can prolong the release of HC under physical conditions and ...

Volatile anesthetics, such as isoflurane, reverse glucose-induced inhibition of pancreatic adenosine triphosphate-sensitive potassium (K(ATP)) channel activity, resulting in reduced insulin secretion and impaired glucose tolerance. No previous studies have investigated the effects of intravenous anesthetics, such as propofol, on pancreatic K(ATP) channels. We investigated the cellular mechanisms underlying the effects ...

The objective of this investigation was to evaluate the test-retest repeatability of insulin sensitivity and secretion indices derived from liquid meal tolerance tests (MTTs) in subjects with normal fasting glucose (NFG) (n = 20), impaired fasting glucose (IFG) (n = 20), or type 2 diabetes mellitus (n = 38). The Matsuda Index of insulin sensitivity and ...

We designed a single unit type controlled release tablet containing nateglinide to decrease both postprandial blood glucose level (PBG) and fasting blood glucose level (FBG) in normal beagle dogs. The tablet contains 60 mg of nateglinide in an immediate release portion, and 90 mg of nateglinide in a controlled release ...

Optical detection of glucose, high drug loading capacity, and self-regulated drug delivery are simultaneously possible using a multifunctional hybrid nanogel particle under a rational design in a colloid chemistry method. Such hybrid nanogels are made of Ag nanoparticle (NP) cores covered by a copolymer gel shell of poly(4-vinylphenylboronic acid-co-2-(dimethylamino)ethyl acrylate) ...

It remains unclear how α-ketoisocaproate (KIC) and leucine are metabolized to stimulate insulin secretion. Mitochondrial BCATm (branched-chain aminotransferase) catalyzes reversible transamination of leucine and α-ketoglutarate to KIC and glutamate, the first step of leucine catabolism. We investigated the biochemical mechanisms of KIC and leucine-stimulated insulin secretion (KICSIS and LSIS, respectively) ...

A series of chromonyl-2,4-thiazolidinediones/imidazolidinediones/2-thioxo-imidazolidine-4-ones (IIIa-i, IVa-i) was prepared by Knoevenagel reaction of 2,4-thiazolidinedione/2,4-imidazolidinedione/2-thioxo-imidazolidine-4-one (IIa-c) with 2/3-formyl chromone (Ia-b) and then alkylation with methyl/ethyl iodide. The prepared compounds were tested for their insulinotropic activities in INS-1 cells. Compounds ıVb and ıVc (at lower concentration, 1 μg/mL) were able to increase insulin release ...

Recent studies have suggested that CRP may interfere with insulin signaling in skeletal muscle and endothelial cells. The aim of this study was to determine whether highly purified CRP increased the rate of glucose appearance in primary hepatocytes in the absence or presence of insulin. Primary rat hepatocytes were provided ...

Pyomyositis is a primary infection of the skeletal muscle, occurring most commonly in tropical countries. Adults who develop the disease have, in most cases, associated comorbidities that compromise the immune system, including diabetes mellitus and liver cirrhosis.

The challenge of this work was to investigate the potential of alginate/chitosan beads containing magnetite nanoparticles as a drug delivery system. The insulin beads were prepared by dripping a solution of sodium alginate containing insulin into a CaCl(2) solution. Magnetite nanoparticles of 5 nm mean size were synthesized inside the ...

Fatty acids, acetylcholine, and GLP-1 enhance insulin secretion in a glucose-dependent manner. However, the interplay between glucose, fatty acids, and the neuroendocrine regulators of insulin secretion is not well understood. Therefore, we studied the acute effects of PA (alone or in combination with glucose, acetylcholine, or GLP-1) on isolated cultured ...

SNAP25 and syntaxin-1 are core proteins of the exocytosis machinery for insulin granules. Takahashi et al. (2010) show that the distribution and kinetics of the SNAP25/syntaxin-1 complex assembly play a key role in regulating the first and second phase of insulin release.

To study the influence of lipid characteristics on the formation, in vitro release, and in vivo absorption of solid lipid nanoparticles (SLN) prepared by the double emulsion method. Stearic acid (SA), octadecyl alcohol (OA), cetyl palmitate (CP), glyceryl monostearate (GM), glyceryl palmitostearate (GP), glyceryl tripalmitate (GT), and glyceryl behenate (GB) ...

AIMS/HYPOTHESES: To investigate the effects of extracellular purines on insulin secretion from mouse pancreatic islets. METHODS: Mouse islets and beta cells were isolated and examined with mRNA real-time quantification, cAMP quantification and insulin and glucagon secretion. ATP release was measured in MIN6c4 cells. Insulin and glucagon secretion were measured in ...

A mechanistic, physiologically-based pharmacokinetic (PK/PD) model was developed to describe the biphasic insulin release and evaluate the racial effects on the glucose-insulin kinetics in response to intravenous glucose. Fifteen African-American and 18 Caucasian children and adolescents between 8 and 18 years of age were enrolled in the study. Intravenous bolus ...

Pulsatile insulin release from glucose-stimulated beta-cells is driven by oscillations of the Ca(2+) and cAMP concentrations in the subplasma membrane space ([Ca(2+)](pm) and [cAMP](pm)). To clarify mechanisms by which cAMP regulates insulin secretion, we performed parallel evanescent wave fluorescence imaging of [cAMP](pm), [Ca(2+)](pm), and phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) in the plasma ...

The cationic, alpha-helical frog skin antimicrobial peptide B2RP (brevinin-2-related peptide) shows sequence similarity to antimicrobial peptides belonging to the brevinin-2 family, but lacks the C-terminal cyclic heptapeptide domain (Cys-Lys-Xaa (4)-Cys). Synthetic B2RP produced a significant (p<0.05) stimulation of insulin release (148% of basal rate at a concentration of 1 muM ...

Succinyl-CoA:3-ketoacid-CoA transferase (SCOT) is a mitochondrial enzyme that catalyzes the reversible transfer of coenzyme-A from acetoacetyl-CoA to succinate to form acetoacetate and succinyl-CoA. mRNAs of SCOT and ATP citrate lyase were decreased 55% and 58% and enzyme activities were decreased >70% in pancreatic islets of the GK rat, a model ...

The AMP-activated protein kinase (AMPK) is one of the key players in cellular energy regulation adapting cellular demands to nutritional and metabolic variations. Oral antidiabetic drugs like metformin and glitazones (thiazolidinediones) are known to stimulate this enzyme. Besides their established action on peripheral organs including liver and muscles, it has ...

In mammals the concentration of blood glucose is kept close to 5 mmol∕l. Different cell types in the islet of Langerhans participate in the control of glucose homeostasis. β-cells, the most frequent type in pancreatic islets, are responsible for the synthesis, storage, and release of insulin. Insulin, released with increases ...

Sulphonylurea drugs have been widely used in the safe and efficacous therapy of type II diabetes during the past five decades. They lower blood glucose predominantly via the stimulation of insulin release from pancreatic beta-cells. However, a moderate insulin-independent regulation of fatty acid esterification and release in adipose tissue cells ...

In non-erythroid cells, insulin stimulates a signal transduction pathway that results in the activation of phosphoinositide 3-kinase (PI3K) and subsequent phosphorylation of phosphodiesterase 3 (PDE3). Erythrocytes possess insulin receptors, PI3K and PDE3B. These cells release adenosine triphosphate (ATP) when exposed to reduced O(2) tension via a signaling pathway that requires ...

Sclerocarya birrea is a plant widely used as traditional medication for the treatment of diabetes in sub-Saharan regions. However, the mechanism of action is unknown and only hypoglycaemic effects of S. birrea extract (SBE) in diabetic rats have been reported to date. Here, we tested aqueous extracts of S. birrea ...

ETHNOPHARMACOLOGICAL RELEVANCE: The radix of Acorus calamus L. (AC) is widely used in the therapy of diabetes in traditional folk medicine of America and Indonesia, and we previously reported the insulin sensitizing activity of the ethyl acetate fraction of AC (ACE). AIM OF THE STUDY: To investigate the insulin releasing ...

Parasympathetic stimulation of pancreatic islets augments glucose-stimulated insulin secretion by inducing inositol trisphosphate receptor (IP(3)R)-mediated calcium ion (Ca2+) release. Ankyrin-B binds to the IP(3)R and is enriched in pancreatic beta cells. We found that ankyrin-B-deficient islets displayed impaired potentiation of insulin secretion by the muscarinic agonist carbachol, blunted carbachol-mediated intracellular ...

Insulin secretion is a complex and highly regulated process. It is well established that cytoplasmic calcium is a key regulator of insulin secretion, but how elevated intracellular calcium triggers insulin granule exocytosis remains unclear, and we have only begun to define the identities of proteins that are responsible for sensing ...

The exhaustibility of in vivo insulin secretion under repeated stimulations was investigated in male Sprague Dawley rats. Eight pulses of either 300 mg/kg glucose (G), or 300 mg/kg glucose plus 0.25 mg/kg forskolin (G+F) were administered for each rat at every 30 min for 4 hours through the jugular vein. ...

Considering restrictive diabetes treatments, new insulin administration strategies constitute a huge medical challenge. This study aimed at developing a new support for insulin reservoirs, using polyelectrolyte multilayer films (PEM films), and thus studying this hormone release in a progressive manner. At first, insulin was loaded in (PDADMAC-PAA)n films, by immerging ...

The physiological response to blood glucose elevation is the pancreatic release of insulin, which blocks hepatic glucose production and release, and stimulates glucose uptake and storage in insulin-dependent tissues. When this first regulatory level is overwhelmed (that is, by exogenous glucose supplementation), persistent hyperglycaemia occurs with intricate consequences related to ...

Glucose-responsive systems are very useful for self-regulated insulin delivery. In this study, glucose-responsive composite microparticles based on chitosan, concanavalin A and dextran were prepared by first fabricating chitosan microparticles subsequently coupling concanavalin A via Schiff-base reaction and dextran layer via specific affinity. SEM, fluorescence microscope, XPS and TGA were used ...

Transfer of reducing equivalents between cytosolic compartments and the mitochondrial matrix is mediated by NADH shuttles. Among these, the malate-aspartate shuttle has been proposed to play a major role in beta-cells for the control of glucose-stimulated insulin secretion. AGC1 or Aralar1 (aspartate-glutamate carrier 1) is a key component of the ...

Adsorption profiles of insulin on porous materials and release profiles of insulin entrapped on folded-sheet mesoporous silica (FSM) were studied. Three types of FSM with different pore sizes (3.0, 6.1, and 9.2 nm) were used as candidates. A simple technique of repeated freezing and thawing resulted in effective adsorption of ...

AIMS/HYPOTHESIS: The aim of the study was to investigate the use of hyperglycaemic clamp tests to identify individuals who will develop diabetes among insulinoma-associated protein-2 antibody (IA-2A)-positive first-degree relatives (IA-2A(+) FDRs) of type 1 diabetic patients. METHODS: Hyperglycaemic clamps were performed in 17 non-diabetic IA-2A(+) FDRs aged 14 to 33 ...

The aim of this research was to develop pH-sensitive insulin-loaded NOCC (N,O-carboxymethyl chitosan) nanoparticles for the controlled release of insulin via the oral route. Thus, in this study, insulin-loaded NOCC nanoparticles were prepared by ionic gelation of NOCC with TPP (tripolyphosphate). NOCC nanoparticles were formed at conditions of 2 mg/ml ...

AIM: The aim of this study was to prepare insulin-loaded poly(lactic acid)-polyethylene glycol microspheres that could control insulin release at least for 1 week and evaluate their in vivo performance in a streptozotocin-induced diabetic rat model. METHODS: The microspheres were prepared using a water-in-oil-in-water double emulsion solvent evaporation technique. Different ...

OBJECTIVES: Diabetes mellitus is a major public health concern in many regions of the world, including the Caribbean. Diabetes is associated with multi-system pathology and central nervous system complications have been receiving increasing attention (dementia, cognitive decline and memory loss). While such pathology has been shown to be associated with ...

The potential of poly 1,3-bis-(p-carboxyphenoxy) propane-co-sebacic acid (p(CPP:SA)) microspheres was investigated for controlled delivery of basal insulin. CPP:SA copolymers with molar compositions of 20:80, 40:60, and 50:50 were synthesized, characterized, and used in the fabrication of microspheres by water-in-oil-in-water double emulsion solvent evaporation technique. Insulin stability was assessed using various ...

Bradykinin causes vasodilation, stimulates tissue-type plasminogen activator (t-PA) release and, in rodents, increases muscle glucose uptake. Although bradykinin causes vasodilation partly by activating nitric-oxide synthase (NOS), the role of nitric oxide in regulating bradykinin-stimulated t-PA release is uncertain. This study examined the effect of high-dose NOS inhibition on bradykinin-stimulated t-PA ...

The inhibitory effect of hydrogen peroxide (H(2)O(2)) on glucose-stimulated insulin secretion was previously reported. However, the precise mechanism involved was not systematically investigated. In this study, the effects of low concentrations of H(2)O(2) (5-10 micromol/L) on glucose metabolism, intracellular calcium ([Ca(2+)](i)) oscillations, and dynamic insulin secretion in rat pancreatic islets ...

Traditional plant treatments have been used throughout the world for the therapy of diabetes mellitus. The aim of the present study was to investigate the efficacy and mode of action of Terminalia bellirica used traditionally for the treatment of diabetes in India. T. bellirica aqueous extract stimulated basal insulin output ...

The aim of this study was to propose novel solid lipid nanoparticles (SLNs) loaded with cell-penetrating peptide (CPP), and to evaluate their potential for oral administration of insulin. Octaarginine (R8) was used as the CPP. SLNs loaded with insulin and R8 (Ra-Ins-SLNs) were prepared using the spontaneous emulsion solvent diffusion ...

Investigations of effective, orally active, and safe antidiabetic metallopharmaceuticals have been carried out during the last two decades. It has been reported that tungsten compounds mimic the action of insulin in intact cell systems. As insulin mimetics, the most investigated tungsten compound was sodium tungstate (ST), rarely investigated was tungstophosphoric ...