Abstract:
:Filtered proteins including insulin are absorbed in the proximal tubule by means of pinocytosis. The first step in this process is binding of the protein to brush border membrane. As it is not known whether absorption exhibits specificity, we set out to determine whether specific binding sites for insulin are present in brush border membranes. Rabbit-isolated brush border membranes were incubated with 125I-insulin and varying concentrations of cold insulin or other peptide hormones. Binding and degradation of 125I-insulin occurred in a time- and temperature-dependent manner. Native insulin competitively inhibited 125I-insulin binding, but calcitonin, arginine vasopressin, glucagon, and growth hormone (10(-6) M) were relatively ineffective. Nonspecific binding averaged one-third of the total radioactivity bound. Scatchard analysis of binding data revealed two classes of insulin receptors: high affinity, low capacity receptors and low affinity, high capacity receptors. Gel filtration analysis of 125I-insulin exposed to brush border membrane revealed the formation of low-molecular-weight products similar to that produced by intact kidneys. The degrading process exhibited some specificity, for cold insulin (10(-6) M) was more effective than calcitonin, vasopressin, glucagon, or growth hormone in inhibiting degradation (32% versus less than 13% inhibition; P less than 0.01). Whether this reflects inhibition of insulin specific binding before exposure to degradation or inhibition of specific enzymes is unclear. In summary, it appears that renal brush border membranes have a major insulin-specific receptor component that could potentially mediate tubular insulin absorption. In addition, there is a smaller nonspecific component that may also have the potential to mediate insulin absorption. Finally, it appears that brush border membranes have the ability to degrade insulin to low-molecular-weight products by a process that exhibits some specificity for insulin.
journal_name
Diabetesjournal_title
Diabetesauthors
Rabkin R,Petersen J,Mamelok Rdoi
10.2337/diab.31.7.618subject
Has Abstractpub_date
1982-07-01 00:00:00pages
618-23issue
7eissn
0012-1797issn
1939-327Xjournal_volume
31pub_type
杂志文章相关文献
DIABETES文献大全abstract::We examined the effects of aldose reductase inhibition (ARI) on glomerular filtration rate (GFR), albuminuria, and kidney histology in partially insulin-treated streptozocin-induced diabetic (STZ-D) rats. After 1 mo of diabetes, GFR was elevated over control values in the STZ-D rats but was not affected by treatment w...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.8.981
更新日期:1989-08-01 00:00:00
abstract::Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD(+)) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that the nicotinic acid derivative acipimox, an NAD(+) precursor, would directly affect mitochondrial f...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2337/db14-0667
更新日期:2015-04-01 00:00:00
abstract::One of the unique features of beta-cells is their relatively low expression of many antioxidant enzymes. This could render beta-cells susceptible to oxidative damage but may also provide a system that is sensitive to reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increase...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1601
更新日期:2007-07-01 00:00:00
abstract::In evaluating therapeutic interventions aimed at preventing diabetic neuropathy, choosing a suitable measure of neural function is difficult, partly because the relation between most available objective measures and the development of symptomatic neuropathy (SN) is unclear. Using data from 67 diabetic patients, we dev...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.35.8.873
更新日期:1986-08-01 00:00:00
abstract:OBJECTIVE:Most pancreatic endocrine cells derive from Ptf1a-expressing progenitor cells. In humans, nonsense mutations in Ptf1a have recently been identified as a cause of permanent neonatal diabetes associated with pancreatic agenesis. The death of Ptf1a-null mice soon after birth has not allowed further insight into ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-1558
更新日期:2008-09-01 00:00:00
abstract::Pulsatile insulin secretion in vivo is believed to be derived, in part, from the intrinsic glucose-dependent intracellular calcium concentration ([Ca2+]i) pulsatility of individual islets. In isolation, islets display fast, slow, or mixtures of fast and slow [Ca2+]i oscillations. We show that the period of islet [Ca2+...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.12.3517
更新日期:2005-12-01 00:00:00
abstract::The presence of the enzyme aldose reductase is increasingly being linked to diabetic complications. The distribution of this enzyme in human cornea, lens, retina, and optic nerve has been studied using specific antibodies against purified human placental aldose reductase raised in both rabbit and goat. The antisera fr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.6.562
更新日期:1984-06-01 00:00:00
abstract::To investigate the early events in insulin signal transmission in liver, isolated rat hepatocytes were labeled with 32P, and proteins phosphorylated in response to insulin were detected by immunoprecipitation with anti-phosphotyrosine and anti-receptor antibodies and analyzed by sodium dodecyl sulfate (SDS)-polyacryla...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.1.66
更新日期:1991-01-01 00:00:00
abstract::Insulin resistance and dysregulation of free fatty acid (FFA) metabolism are core defects in type 2 diabetic (T2DM) and obese normal glucose tolerant (NGT) individuals. Impaired muscle mitochondrial function (reduced ATP synthesis) also has been described in insulin-resistant T2DM and obese subjects. We examined wheth...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1130
更新日期:2014-08-01 00:00:00
abstract::Obesity is increasing, yet despite the necessity of maintaining muscle mass and function with age, the effect of obesity on muscle protein turnover in older adults remains unknown. Eleven obese (BMI 31.9 ± 1.1 kg · m(-2)) and 15 healthy-weight (BMI 23.4 ± 0.3 kg · m(-2)) older men (55-75 years old) participated in a s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0021
更新日期:2015-09-01 00:00:00
abstract::We previously reported a syndrome of severe hyperinsulinemia and early-onset hypertension in three patients with dominant-negative mutations in the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR)-gamma. We now report the results of further detailed pathophysiological evaluation of these subj...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.4.910
更新日期:2003-04-01 00:00:00
abstract:OBJECTIVE:Recent work has shown that insulin stimulates its own secretion in insulin-sensitive humans, suggesting that insulin resistance in the β-cell could cause β-cell dysfunction. We have tested whether insulin exposure and insulin sensitivity modulate β-cell function in subjects with normal glucose tolerance (NGT)...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/db11-0827
更新日期:2011-12-01 00:00:00
abstract::Although recent studies show that adipose tissue macrophages (ATMs) participate in the inflammatory changes in obesity and contribute to insulin resistance, the properties of these cells are not well understood. We hypothesized that ATMs recruited to adipose tissue during a high-fat diet have unique inflammatory prope...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1076
更新日期:2007-01-01 00:00:00
abstract::Cyclic nucleotide phosphodiesterase (PDE) 3B plays an important role in the antilipolytic action of insulin and, thereby, the release of fatty acids from adipocytes. Increased concentrations of circulating fatty acids as a result of elevated or unrestrained lipolysis cause insulin resistance. The lipolytic action of t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.3.631
更新日期:2002-03-01 00:00:00
abstract::Enteroviruses have been examined for their possible role in the etiology of IDDM for nearly 40 years, yet the evidence remains inconclusive. The mechanism of acute cytolytic infection of beta-cells, proposed by earlier studies, appears to be incompatible with the long preclinical period of autoimmunity preceding IDDM....
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.46.2.161
更新日期:1997-02-01 00:00:00
abstract::Carbohydrate-responsive element-binding protein (ChREBP) is a glucose-sensing transcription factor required for glucose-stimulated proliferation of pancreatic β-cells in rodents and humans. The full-length isoform (ChREBPα) has a low glucose inhibitory domain (LID) that restrains the transactivation domain when glucos...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0239
更新日期:2015-12-01 00:00:00
abstract::Poorly controlled insulin-dependent diabetes mellitus (IDDM) is associated with elevated basal plasma growth hormone (GH), disproportionally low insulin-like growth factor I (IGF-I) levels, and impaired somatic growth. These derangements in the GH-IGF axis imply a state of GH resistance. The mechanism of GH resistance...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.5.605
更新日期:1992-05-01 00:00:00
abstract:OBJECTIVE:Recently, several drugs have been shown to exert beneficial effects for metabolic syndrome through mild regulation of mitochondrial function. Hence, we explored a strategy of targeting mitochondrial function to improve glucose and lipid metabolism. RESEARCH DESIGN AND METHODS:Mitochondrial membrane potential...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0223
更新日期:2010-01-01 00:00:00
abstract::This study examines whether the loss of metabolic control in initially normalized islet transplants can result from the inadequate composition of the donor tissue. Streptozotocin-induced diabetic rats were followed for 64 weeks after the intraportal injection of islet isografts with different composition. The implanta...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.12.1814
更新日期:1996-12-01 00:00:00
abstract::It is suggested that the maternal transmission of islet autoantibodies increases the risk of autoimmune diabetes in mice. The aim of this study was to determine whether fetal exposure to islet autoantibodies modified the risk of type 1 diabetes in humans. Islet autoantibodies were measured at birth in 720 offspring of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.1.1
更新日期:2004-01-01 00:00:00
abstract::Liver fat accumulation is proposed to link obesity and insulin resistance. To dissect the role of liver fat in the insulin resistance of diet-induced obesity, we altered liver fat using a choline-deficient diet. C57Bl/6 mice were fed a low-fat (10% of calories) or high-fat (45% of calories) diet for 8 weeks; during th...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0097
更新日期:2006-07-01 00:00:00
abstract::Enteroendocrine cells (EECs) produce hormones such as glucagon-like peptide 1 and peptide YY that regulate food absorption, insulin secretion, and appetite. Based on the success of glucagon-like peptide 1-based therapies for type 2 diabetes and obesity, EECs are themselves the focus of drug discovery programs to enhan...
journal_title:Diabetes
pub_type: 评论,杂志文章
doi:10.2337/db18-0883
更新日期:2019-05-01 00:00:00
abstract::The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is ubiquitously distributed in both the central and peripheral nervous systems and exerts a variety of effects. PACAP is a neuropeptide in pancreatic islets, where it has been suggested as a parasympathetic and sensory neurotransmitter. PACAP ...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.50.9.1959
更新日期:2001-09-01 00:00:00
abstract::We have produced a monoclonal antibody 3A4 to the surface of islet cells by fusing spleen lymphocytes from nonobese diabetic (NOD) mice. To identify the molecular weight of specific target antigens reacting with 3A4, 125I-surface-labeled In-111 insulinoma cells were solubilized and extracts were absorbed with 3A4, and...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.35.5.517
更新日期:1986-05-01 00:00:00
abstract::Growth differentiation factor 11 (GDF11) has been shown to promote stem cell activity and rejuvenate the function of multiple organs in old mice, but little is known about the functions of GDF11 in the diabetic rat model of hindlimb ischemia. In this study, we found that systematic replenishment of GDF11 rescues angio...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1583
更新日期:2018-10-01 00:00:00
abstract::The Diabetes Association of greater Cleveland screened 307,000 individuals in the metropolitan area for diabetes with a 75-gm. oral load of carbohydrate. Of these subjects 12,600 (4.1 per cent) had a two-capillary blood glucose level of greater than 139 mg. per cent and were defined as positive. Seventy per cent of th...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.25.12.1110
更新日期:1976-12-01 00:00:00
abstract::Twelve type I (insulin-dependent) diabetic subjects in stable metabolic control for at least 3 mo received a controlled diet containing 50% carbohydrate, 35% fat, and 15% protein. Calorie intake varied from 1800 to 2200 calories, depending on individual needs. Part of the polyunsaturated omega-6 fatty acids (omega 6FA...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.11.1412
更新日期:1989-11-01 00:00:00
abstract::beta-Cell cycle progression and proliferation are critical to maintain beta-cell mass in adult mice. Of the cell cycle inhibitors, p27Kip1 is thought to be the primary modulator of the proliferative status in most cell types. p27 plays a role in beta-cell adaptation in genetic models of insulin resistance. To study th...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0861
更新日期:2006-12-01 00:00:00
abstract::Although diabetes is the most common cause of end-stage renal disease (ESRD) worldwide, most people with diabetic nephropathy will never develop ESRD but will instead die of cardiovascular (CV) disease (CVD). The first evidence of kidney injury in diabetes is often microalbuminuria, itself also an independent risk mar...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-0795
更新日期:2013-11-01 00:00:00
abstract::A 21-year-old female patient complaining of frequent hypoglycemic attacks in the presence of a large amount of circulating insulin-binding antibodies without previous known immunization is described. In order to clarify the possible mechanism of the hypoglycemic attacks occurring in this new syndrome, changes in plasm...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.5.500
更新日期:1977-05-01 00:00:00