Induction of resistance to endothelin-1's biochemical actions by elevated glucose levels in retinal pericytes

Chemerin is an adipose-derived signaling protein (adipokine) that regulates adipocyte differentiation and function, immune function, metabolism, and glucose homeostasis through activation of chemokine-like receptor 1 (CMKLR1). A second chemerin receptor, G protein-coupled receptor 1 (GPR1) in mammals, binds chemerin with an affinity similar to CMKLR1; however, the function of GPR1 in mammals is essentially unknown. Herein, we report that expression of murineGpr1mRNA is high in brown adipose tissue and white adipose tissue (WAT) and skeletal muscle. In contrast to chemerin (Rarres2) andCmklr1,Gpr1expression predominates in the non-adipocyte stromal vascular fraction of WAT. Heterozygous and homozygousGpr1-knockout mice fed on a high-fat diet developed more severe glucose intolerance than WT mice despite having no difference in body weight, adiposity, or energy expenditure. Moreover, mice lackingGpr1exhibited reduced glucose-stimulated insulin levels and elevated glucose levels in a pyruvate tolerance test. This study is the first, to our knowledge, to report the effects ofGpr1deficiency on adiposity, energy balance, and glucose homeostasisin vivo. Moreover, these novel results demonstrate that GPR1 is an active chemerin receptor that contributes to the regulation of glucose homeostasis during obesity.

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Plasma glucose levels and outcome after aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/jns.1993.79.6.0885 ◽

1993 ◽

Vol 79 (6) ◽

pp. 885-891 ◽

Cited By ~ 87

Author(s):

Giuseppe Lanzino ◽

Neal F. Kassell ◽

Teresa Germanson ◽

Laura Truskowski ◽

Wayne Alves

Keyword(s):

Subarachnoid Hemorrhage ◽

Plasma Glucose ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Ct Scans ◽

Good Recovery ◽

Glucose Levels ◽

Poor Outcome ◽

Elevated Glucose ◽

Mean Glucose

✓ Plasma glucose levels were studied in 616 patients admitted within 72 hours after subarachnoid hemorrhage (SAH). Glucose levels measured at admission showed a statistically significant association with Glasgow Coma Scale scores, Botterell grade, deposition of blood on computerized tomography (CT) scans, and level of consciousness at admission. Elevated glucose levels at admission predicted poor outcome. A good recovery, as assessed by the Glasgow Outcome Scale at 3 months, occurred in 70.2% of patients with normal glucose levels (≤ 120 mg/dl) and in 53.7% of patients with hyperglycemia (> 120 mg/dl) (p = 0.002). The death rates for these two groups were 6.7% and 19.9%, respectively (p = 0.001). The association was still maintained after adjusting for age (> or ≤ 50 years) and thickness of clot on CT scans (thin or thick) in the subset of patients who were alert/drowsy at admission. Increased mean glucose levels between Days 3 and 7 also predicted a worse outcome; good recovery was observed in 132 (73.7%) of 179 patients who had normal mean glucose levels (≤ 120 mg/dl) and 160 (49.7%) of 322 who had elevated mean glucose levels (> 120 mg/dl) (p < 0.0001). Death occurred in 6.7% and 20.8% of the two groups, respectively (p < 0.0001). It is concluded that admission plasma glucose levels can serve as an objective prognostic indicator after SAH. Elevated glucose levels during the 1st week after SAH also predict a poor outcome. However, a causal link between hyperglycemia and outcome after delayed cerebral ischemia, although suggested by experimental data, cannot be established on the basis of this study.

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Successful Continuation of Peritoneal Dialysis after "Sweet" Hydrothorax

BANTAO Journal ◽

10.1515/bj-2015-0009 ◽

2015 ◽

Vol 13 (1) ◽

pp. 42-45

Author(s):

Utku Erdem Soyaltin ◽

Ferhat Ekinci ◽

Denizhan Ayatan ◽

Cihangir Turemis ◽

Mustafa Yildirim ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Glucose Concentration ◽

Serum Glucose ◽

X Ray ◽

Glucose Levels ◽

Low Protein ◽

Elevated Glucose ◽

Chest X Ray ◽

Stage Renal Disease ◽

End Stage

AbstractA 44-year-old woman with end-stage renal disease presented with dyspnea on exertion and a vague chest pain about two weeks after commencing continuous ambulatory peritoneal dialysis (CAPD) four months ago. A chest x-ray revealed massive unilateral right-sided pleural effusion. Laboratory analysis of the effusion revealed low protein and lactate dehydrogenase but elevated glucose levels were consistent with transudate and pleuroperitoneal leakage. Pleural glucose concentration was much higher than patients’ serum glucose concentration, which was suggestive of "sweet" hydrothorax because of this high glucose concentration. It is advisable to keep this condition in mind among the differenttial diagnoses of hydrothorax in patients on CAPD.

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Bottom-up proteomics analysis of the secretome of murine islets of Langerhans in elevated glucose levels

The Analyst ◽

10.1039/c6an02268e ◽

2017 ◽

Vol 142 (2) ◽

pp. 284-291 ◽

Cited By ~ 1

Author(s):

Andrew Schmudlach ◽

Jeremy Felton ◽

Robert T. Kennedy ◽

Norman J. Dovichi

Keyword(s):

Type 2 Diabetes ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Oxidative Damage ◽

Islets Of Langerhans ◽

High Glucose ◽

Proteomics Analysis ◽

Glucose Levels ◽

Elevated Glucose

Glucotoxicity is a causative agent of type-2 diabetes, where high glucose levels damage the islets of Langerhans resulting in oxidative damage and endoplasmic reticulum stress.

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Glucose stimulates somatostatin secretion in pancreatic δ-cells by cAMP-dependent intracellular Ca2+ release

The Journal of General Physiology ◽

10.1085/jgp.201912351 ◽

2019 ◽

Vol 151 (9) ◽

Cited By ~ 4

Author(s):

Geoffrey Denwood ◽

Andrei Tarasov ◽

Albert Salehi ◽

Elisa Vergari ◽

Reshma Ramracheya ◽

...

Keyword(s):

Electrical Activity ◽

Secretory Vesicles ◽

Glucose Levels ◽

Somatostatin Secretion ◽

Elevated Glucose ◽

Mouse Islets ◽

Underlying Mechanisms ◽

Fold Stimulation ◽

Cyclase Activator ◽

Stimulation Of

Somatostatin secretion from pancreatic islet δ-cells is stimulated by elevated glucose levels, but the underlying mechanisms have only partially been elucidated. Here we show that glucose-induced somatostatin secretion (GISS) involves both membrane potential-dependent and -independent pathways. Although glucose-induced electrical activity triggers somatostatin release, the sugar also stimulates GISS via a cAMP-dependent stimulation of CICR and exocytosis of somatostatin. The latter effect is more quantitatively important and in mouse islets depolarized by 70 mM extracellular K+, increasing glucose from 1 mM to 20 mM produced an ∼3.5-fold stimulation of somatostatin secretion, an effect that was mimicked by the application of the adenylyl cyclase activator forskolin. Inhibiting cAMP-dependent pathways with PKI or ESI-05, which inhibit PKA and exchange protein directly activated by cAMP 2 (Epac2), respectively, reduced glucose/forskolin-induced somatostatin secretion. Ryanodine produced a similar effect that was not additive to that of the PKA or Epac2 inhibitors. Intracellular application of cAMP produced a concentration-dependent stimulation of somatostatin exocytosis and elevation of cytoplasmic Ca2+ ([Ca2+]i). Both effects were inhibited by ESI-05 and thapsigargin (an inhibitor of SERCA). By contrast, inhibition of PKA suppressed δ-cell exocytosis without affecting [Ca2+]i. Simultaneous recordings of electrical activity and [Ca2+]i in δ-cells expressing the genetically encoded Ca2+ indicator GCaMP3 revealed that the majority of glucose-induced [Ca2+]i spikes did not correlate with δ-cell electrical activity but instead reflected Ca2+ release from the ER. These spontaneous [Ca2+]i spikes are resistant to PKI but sensitive to ESI-05 or thapsigargin. We propose that cAMP links an increase in plasma glucose to stimulation of somatostatin secretion by promoting CICR, thus evoking exocytosis of somatostatin-containing secretory vesicles in the δ-cell.

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Euglycemic Diabetic Ketoacidosis in Pregnancy: A Case Report and Review of Current Literature

Case Reports in Critical Care ◽

10.1155/2019/8769714 ◽

2019 ◽

Vol 2019 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Johnny F. Jaber ◽

Matthew Standley ◽

Raju Reddy

Keyword(s):

Blood Glucose ◽

Diabetic Ketoacidosis ◽

Case Reports ◽

Anion Gap ◽

Fetal Mortality ◽

Glucose Levels ◽

Elevated Glucose ◽

High Doses ◽

Euglycemic Diabetic Ketoacidosis ◽

In Pregnancy

Diabetic ketoacidosis (DKA) in pregnancy is associated with high fetal mortality rates. A small percentage of DKA occurs in the absence of high glucose levels seen in traditional DKA. Prompt recognition and management is crucial. We report a case of a 30-year-old pregnant woman with type 1 diabetes mellitus admitted with euglycemic DKA (blood glucose <200 mg/dL). Initial laboratory testing revealed a severe anion gap acidosis with pH 7.11, anion gap 23, elevated β-hydroxybutyric acid of 9.60 mmol/L, and a blood glucose of 183 mg/dL—surprisingly low given her severe acidosis. The ketoacidosis persisted despite high doses of glucose and insulin infusions. Due to nonresolving acidosis, her hospital course was complicated by spontaneous intrauterine fetal demise. Euglycemia and severe acidosis continued to persist until delivery of fetus and placenta occurred. It was observed that the insulin sensitivity dramatically increased after delivery of fetus and placenta leading to rapid correction of ketoacidosis. This case highlights that severe ketonemia can occur despite the absence of severely elevated glucose levels. We discuss the mechanism that leads to this pathophysiologic state and summarize previously published case reports about euglycemic DKA in pregnancy.

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