Abstract:
:Glucagon-like peptide 1 receptor (GLP-1R) imaging with radiolabeled exendin has proven to be a powerful tool to quantify β-cell mass (BCM) in vivo. As GLP-1R expression is thought to be influenced by glycemic control, we examined the effect of blood glucose (BG) levels on GLP-1R-mediated exendin uptake in both murine and human islets and its implications for BCM quantification. Periods of hyperglycemia significantly reduced exendin uptake in murine and human islets, which was paralleled by a reduction in GLP-1R expression. Detailed mapping of the tracer uptake and insulin and GLP-1R expression conclusively demonstrated that the observed reduction in tracer uptake directly correlates to GLP-1R expression levels. Importantly, the linear correlation between tracer uptake and β-cell area was maintained in spite of the reduced GLP-1R expression levels. Subsequent normalization of BG levels restored absolute tracer uptake and GLP-1R expression in β-cells and the observed loss in islet volume was halted. This manuscript emphasizes the potency of nuclear imaging techniques to monitor receptor regulation noninvasively. Our findings have significant implications for clinical practice, indicating that BG levels should be near-normalized for at least 3 weeks prior to GLP-1R agonist treatment or quantitative radiolabeled exendin imaging for BCM analysis.
journal_name
Diabetesjournal_title
Diabetesauthors
Buitinga M,Cohrs CM,Eter WA,Claessens-Joosten L,Frielink C,Bos D,Sandker G,Brom M,Speier S,Gotthardt Mdoi
10.2337/db20-0616subject
Has Abstractpub_date
2020-11-01 00:00:00pages
2246-2252issue
11eissn
0012-1797issn
1939-327Xpii
db20-0616journal_volume
69pub_type
杂志文章相关文献
DIABETES文献大全abstract::Neonatal morbidity was assessed in the offspring of 878 mothers with gestational diabetes mellitus (GDM), 132 mothers with pre-GDM, and 380 control subjects. Compared with the control group, the GDM group had a higher incidence of complications, including macrosomia, hypoglycemia, hyperbilirubinemia, hypocalcemia, pol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.2.s74
更新日期:1991-12-01 00:00:00
abstract::The effect of elevated glucagon concentrations on insulin requirements and on blood glucose concentrations was studied in five insulin-requiring diabetic subjects during feedback control of hyperglycemia with an automated glucose-controlled insulin infusion system (artificial endocrine pancreas) for six to eight hours...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.6.649
更新日期:1978-06-01 00:00:00
abstract::Dietary methionine restriction (MR) produces a rapid and persistent remodeling of white adipose tissue (WAT), an increase in energy expenditure (EE), and enhancement of insulin sensitivity. Recent work established that hepatic expression of FGF21 is robustly increased by MR. Fgf21-/- mice were used to test whether FGF...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1212
更新日期:2017-04-01 00:00:00
abstract::Recently, we identified in normally type 1 diabetes-prone NOD/LtJ mice a spontaneous new leptin receptor (LEPR) mutation (designated Lepr(db-5J)) producing juvenile obesity, hyperglycemia, hyperinsulinemia, and hyperleptinemia. This early type 2 diabetes syndrome suppressed intra-islet insulitis and permitted spontane...
journal_title:Diabetes
pub_type: 杂志文章
doi:
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:Common variants in the gene TCF7L2 confer the largest effect on the risk of type 2 diabetes. The present study was undertaken to increase our understanding of the mechanisms by which this gene affects type 2 diabetes risk. RESEARCH DESIGN AND METHODS:Eight subjects with risk-conferring TCF7L2 genotypes (TT o...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1169
更新日期:2010-02-01 00:00:00
abstract::Tight glycemic control by intensive insulin therapy effectively delays the onset and slows the progression of diabetic complications but is associated with frequent dose adjustments and a high incidence of hypoglycemia. Successful pancreas transplantation corrects abnormal glucose metabolism but subjects patients to m...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.3.342
更新日期:1996-03-01 00:00:00
abstract::Congenital malformations occur more frequently in the offspring of diabetic mothers. These in vivo and in vitro studies investigate the potential adverse effects of hyperglycemia on kidney development in the rat. Female rats were made hyperglycemic throughout gestation with a single injection of streptozotocin (STZ) o...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.11.2240
更新日期:1999-11-01 00:00:00
abstract::Although ATP-binding cassette transporter A1 (ABCA1) is well known for its role in cholesterol efflux and HDL formation, it is expressed in various tissues, where it may have different functions. Because hypoalphalipoproteinemia is highly prevalent in Mexico, we screened the ABCA1 coding sequence in Mexican individual...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0905
更新日期:2007-07-01 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::Myocardial dysfunction, perfusion abnormalities, and the extent to which these abnormalities may be reversed by C-peptide administration was assessed in type 1 diabetic patients. Eight patients were studied before and during a 0.84-mg/kg dipyridamole administration using a randomized double-blind crossover protocol wi...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diabetes.51.10.3077
更新日期:2002-10-01 00:00:00
abstract::Rats with classic Goldblatt (two-kidney) hypertension had diabetes induced by streptozotocin. After four months of diabetes, glomeruli of the unclipped kidney of hypertensive diabetic rats had markedly increased diabetic changes, including mesangial matrix thickening and mesangial immunoglobulin (IgG and IgM) and comp...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.7.738
更新日期:1978-07-01 00:00:00
abstract::Chronic high-fat feeding in rats induces profound whole-body insulin resistance, mainly due to effects in oxidative skeletal muscle. The mechanisms of this reaction remain unclear, but local lipid availability has been implicated. The aim of this study was to examine the influence of three short-term physiological man...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.12.2022
更新日期:1997-12-01 00:00:00
abstract::Low birth weight is a well-established risk factor for type 2 diabetes, but the risk at high birth weight levels remains uncertain. Potential sex differences in the associations are unexplored. We investigated whether sex influences the association of birth weight and adult type 2 diabetes, using a cohort of 113,801 m...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0494
更新日期:2015-12-01 00:00:00
abstract::The nutrient-sensitive kinase mammalian target of rapamycin (mTOR) and its downstream target S6 kinase (S6K) are involved in amino acid-induced insulin resistance. Whether the mTOR/S6K pathway directly modulates glucose metabolism in humans is unknown. We studied 11 healthy men (29 years old, BMI 23 kg/m(2)) twice in ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1016
更新日期:2007-06-01 00:00:00
abstract::This article examines the role of the autonomic nervous system in mediating the increase of glucagon secretion observed during insulin-induced hypoglycemia (IIH). In the first section, we briefly review the importance of the alpha-cell response in recovery from hypoglycemia under both physiologic conditions and pathop...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.47.7.995
更新日期:1998-07-01 00:00:00
abstract::Diet-induced obesity is the primary determinant of the current epidemic of diabetes. We have explored the role of genetics in this phenomenon, using C57Bl/6 (B6), 129S6/SvEvTac (129), and intercross (B6 x 129)F2 mice on a low- or high-fat diet. Over an 18-week period, B6 and F2 mice gained more weight, had higher leve...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.12.3274
更新日期:2004-12-01 00:00:00
abstract::Studies have been carried out on activities of lysosomal beta-N-acetylhexosaminidase (hex), beta-galactosidase (beta-gal), alpha-glucosidase (alpha-glu), and acid phosphatase (AP) in serum and urine from patients with juvenile diabetes and matched controls. There is a large increase in blood and urinary hex activity (...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.25.5.420
更新日期:1976-05-01 00:00:00
abstract::Glucose controls islet beta-cell mass and function at least in part through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway downstream of insulin signaling. The Foxo proteins, transcription factors known in other tissues to be negatively regulated by Akt activation, affect proliferation and metabolism. In this st...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db05-0678
更新日期:2006-06-01 00:00:00
abstract::Impaired wound healing is one of the main causes of diabetic foot ulcerations. However, the exact mechanism of delayed wound healing in diabetes is not fully understood. Long noncoding RNAs (lncRNAs) are widely involved in a variety of biological processes and diseases, including diabetes and its associated complicati...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0147
更新日期:2020-10-01 00:00:00
abstract::Studies were conducted to clarify the relationship between the external fatty acid concentration and glucagon in the regulation of hepatic fatty acid metabolism. Hepatocytes from fed rats were incubated with increasing concentrations of oleate (up to 1 mM) in the presence and absence of glucagon and the time sequence ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.3.236
更新日期:1980-03-01 00:00:00
abstract::We describe an automated method for the isolation of human pancreatic islets. The procedure meets the following requirements: 1) minimal traumatic action on the islets, 2) continuous digestion in which the islets that are progressively liberated can be saved from further enzymatic action, 3) minimal human intervention...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.4.413
更新日期:1988-04-01 00:00:00
abstract::Leptin, the product of the OB gene, is increased in obese individuals, suggesting resistance to its effect. We questioned whether subjects with NIDDM have an altered regulation of serum leptin levels. We used a radioimmunoassay to measure serum leptin levels in three groups from the San Antonio Heart Study: 1) 50 Mexi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.6.822
更新日期:1996-06-01 00:00:00
abstract::RIN-m cells, cultured from a rat insulinoma, not only bind and secrete but also degrade insulin (Diabetes 1982; 31:521-31). The insulin-degrading activity resides in the cytosol and is similar to the insulin-specific proteases previously described in muscle and other tissues. It has an apparent Km of 0.15 microM for p...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.2.121
更新日期:1985-02-01 00:00:00
abstract::Insulin stimulation of adipose and muscle cells results in the translocation of GLUT4 from an intracellular location to the plasma membrane; this translocation is defective in insulin resistance. Studies have suggested an important role for synaptobrevin and syntaxin homologues in this event, particularly the v-solubl...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.4.618
更新日期:2000-04-01 00:00:00
abstract:OBJECTIVE:We hypothesized that intranasal insulin (I-I) delivery targets the nervous system while avoiding potential adverse systemic effects when compared with subcutaneous insulin (S-I) for experimental streptozotocin-induced diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS:I-I or S-I at 0.87 IU dai...
journal_title:Diabetes
pub_type: 杂志文章,收录出版
doi:10.2337/db08-1287
更新日期:2009-04-01 00:00:00
abstract::Hyperglycemia upon hospital admission in patients with ST-segment elevation myocardial infarction (STEMI) occurs frequently and is associated with adverse outcomes. It is, however, unsettled as to whether an elevated blood glucose level is the cause or consequence of increased myocardial damage. In addition, whether t...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db13-1849
更新日期:2014-07-01 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::Fed male Wistar rats were eviscerated by two procedures. The first group of eviscerated rats were left with a nonfunctional liver in situ while the second group were eviscerated by a newer technic, developed in this laboratory, that preserves liver function. The animals were maintained on a regimen of saline and antib...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.7.637
更新日期:1975-07-01 00:00:00
abstract::Two previously described pedigrees with familial hyperproinsulinemia have elevated proinsulin conversion intermediates resulting from amino acid substitutions in the proinsulin molecule. In contrast, a third family with elevated levels of an apparently normal proinsulin molecule may have a defect in the converting pro...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.8.821
更新日期:1985-08-01 00:00:00
abstract::Munc13-1 is a diacylglycerol (DAG) receptor that is essential for synaptic vesicle priming. We recently showed that Munc13-1 is expressed in rodent and human islet beta-cells and that its levels are reduced in islets of type 2 diabetic humans and rat models, suggesting that Munc13-1 deficiency contributes to the abnor...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db05-1263
更新日期:2006-05-01 00:00:00