Once-Weekly Semaglutide Use in Type 2 Diabetes: Real-World Data from the SURE Netherlands Observational Study.

Introduction: SURE Netherlands (NCT03929679) evaluated the use of once-weekly (OW) semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), in routine clinical care for individuals with type 2 diabetes (T2D).

Methods: Adults (age ≥ 18 years) with T2D were enrolled into the single-arm study. The primary endpoint was change from baseline to end of study (EOS;  approx.

The insulin-like growth factor-I receptor stimulating activity (IRSA) in health and disease.

Determination of true IGF-I bioactivity in serum and other biological fluids is still a substantial challenge. The IGF-IR Kinase Receptor Activation assay (IGF-IR KIRA assay) is a novel tool to asses IGF-IR stimulating activity (IRSA) and has opened a new era in studying the IGF system. In this paper we discuss many studies showing that measuring IRSA by the IGF-IR KIRA assay often provides fundamentally different information about the IGF system than the commonly used total IGF-I immunoassays.

Revisiting the Role of Insulin-Like Growth Factor-I Receptor Stimulating Activity and the Apolipoprotein E in Alzheimer's Disease.

: Alterations in insulin-like growth factor I (IGF-I) signaling have been associated with dementia and Alzheimer's disease (AD). Studies on the association between IGF-I levels and dementia risk have been inconclusive. We reported earlier that higher levels of IGF-I receptor stimulating activity are associated with a higher prevalence and incidence of dementia.

Effects of Somatostatin Analogs and Dopamine Agonists on Insulin-Like Growth Factor 2-Induced Insulin Receptor Isoform A Activation by Gastroenteropancreatic Neuroendocrine Tumor Cells.

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) express insulin-like growth factor (IGF)-related factors [IGF1, IGF2; insulin receptor (IR)-A, IR-B; IGF-binding protein (IGFBP) 1-3] as well as somatostatin (SSTRs) and dopamine D2 receptors (D2Rs).

Objectives: To (1) compare mRNA expression of IGF-related factors in human pancreatic NET (panNET) cell lines with that in human GEP-NETs to evaluate the usefulness of these cells as a model for studying the IGF system in GEP-NETs, (2) determine whether panNET cells produce growth factors that activate IR-A, and (3) investigate whether somatostatin analogs (SSAs) and/or dopamine agonists (DAs) influence the production of these growth factors.

Methods: In panNET cells (BON-1 and QGP-1) and GEP-NETs, mRNA expression of IGF-related factors was measured by quantitative real-time PCR.

Somatostatin analogues for receptor targeted photodynamic therapy.

Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells.

Insulin-like growth factor-I receptor stimulating activity is associated with dementia.

Background: Insulin-like growth factor-I (IGF-I) is a pleiotropic hormone. Several studies have related IGF-I levels to dementia, but evidence remains inconclusive. IGF-I receptor stimulating activity is a more direct measure of biologically available IGF-I than total IGF-I levels.

Low circulating IGF-I bioactivity is associated with human longevity: findings in centenarians' offspring.

Unlabelled: Centenarians' offspring represent a suitable model to study age-dependent variables (e.g. IGF-I) potentially involved in the modulation of the lifespan.

Circulating insulin-like growth factors may contribute substantially to insulin receptor isoform A and insulin receptor isoform B signalling.

Background: Only a fraction of circulating insulin-like activity is due to insulin itself. The aim of this study was to determine total serum insulin-like activity mediated via the insulin receptor isoform A (IR-A) and isoform B (IR-B) by using kinase receptor activation (KIRA) assays specific for the IR-A and IR-B.

Methods: The IR-A and IR-B KIRA assays use human embryonic kidney cells which have been transfected with the human IR-A or IR-B gene and quantify serum-mediated phosphorylation of the IR.

High IGFBP2 levels are not only associated with a better metabolic risk profile but also with increased mortality in elderly men.

Objective: Serum IGF-binding protein 2 (IGFBP2) concentrations are reduced in obese humans and increase after a prolonged period of fasting. We investigated the association between IGFBP2 levels and mortality together with other factors that are related to IGFBP2, including the metabolic syndrome and physical function.

Design: A prospective observational study at a clinical research center of 403 independently living elderly men (aged 73-94 years).

Effect of intensive insulin therapy on the somatotropic axis of critically ill children.

Context: Intensive insulin therapy (IIT) improved outcome in the adult and pediatric intensive care unit (PICU) compared with conventional insulin therapy (CIT). IIT did not increase the anabolic hormone IGF-I in critically ill adults, but feeding in critically ill children and pediatric hormonal responses may differ. Twenty-five percent of the children with IIT experienced hypoglycemia, which may have evoked counterregulatory responses.

Insulin glargine is more potent in activating the human IGF-I receptor than human insulin and insulin detemir.

Objective: To investigate whether human insulin (HI) and insulin analogues differ in their ability to activate the human IGF-I receptor (IGF-IR), the human insulin receptor A (IR-A) and the human insulin receptor B (IR-B) in vitro.

Methods: HI, short-acting insulin analogues (insulin aspart; insulin lispro) and long-acting insulin analogues (insulin glargine; insulin detemir) were compared by using kinase receptor activation (KIRA) bioassays specific for IGF-IR, IR-A or IR-B, respectively. These assays quantify ligand activity by measuring receptor auto-phosphorylation upon ligand binding.

Igf-I bioactivity in an elderly population: relation to insulin sensitivity, insulin levels, and the metabolic syndrome.

Objective: There is a complex relationship between IGF-I, IGF binding proteins, growth hormone, and insulin. The IGF-I kinase receptor activation assay (KIRA) is a novel method for measuring IGF-I bioactivity in human serum. We speculated that determination of IGF-I bioactivity might broaden our understanding of the IGF-I system in subjects with the metabolic syndrome.

Bioactive rather than total IGF-I is involved in acute responses to nutritional interventions in CAPD patients.

Background: Inadequate food intake plays an important role in the development of malnutrition in continuous ambulatory peritoneal dialysis (CAPD) patients. Aim of the study. The aim of the study was to investigate in CAPD patients whether circulating insulin-like growth factor-I (IGF-I) bioactivity may offer a more sensitive index to acute nutritional interventions than total IGF-I.

Heterophilic antibodies may be a cause of falsely low total IGF1 levels.

Background: A low serum total IGF1 is considered as a diagnostic indicator of GH deficiency (GHD) in the presence of hypopituitarism. Introduction of IRMA and chemiluminescent immunometric assay (CLIA) IGF1 immunoassays has introduced endogenous antibodies as a new source of interference. In general, this goes unnoticed and might lead to unnecessary diagnostic and therapeutic interventions.

Low circulating insulin-like growth factor I bioactivity in elderly men is associated with increased mortality.

Context: Low IGF-I signaling activity prolongs lifespan in certain animal models, but the precise role of IGF-I in human survival remains controversial. The IGF-I kinase receptor activation assay is a novel method for measuring IGF-I bioactivity in human serum. We speculated that determination of circulating IGF-I bioactivity is more informative than levels of immunoreactive IGF-I.

Normal values of circulating insulin-like growth factor-I bioactivity in the healthy population: comparison with five widely used IGF-I immunoassays.

Background: IGF-I immunoassays are primarily used to estimate IGF-I bioactivity. Recently an IGF-I-specific kinase receptor activation assay (KIRA) has been developed as an alternative method. However, no normative values have been established for the IGF-I KIRA.