Urinary metal profiles in mother-offspring pairs and their association with early dysglycemia in the International Hyperglycemia and Adverse Pregnancy Outcome Follow Up Study (HAPO-FUS).

Background: Variations in dietary intake and environmental exposure patterns of essential and non-essential trace metals influence many aspects of human health throughout the life span.

Objective: To examine the relationship between urine profiles of essential and non-essential metals in mother-offspring pairs and their association with early dysglycemia.

Methods: Herein, we report findings from an ancillary study to the international Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study (HAPO-FUS) that examined urinary essential and non-essential metal profiles from mothers and offspring ages 10-14 years (1012 mothers, 1013 offspring, 968 matched pairs) from 10 international sites.

A novel chronic in vivo oral cadmium exposure-washout mouse model for studying cadmium toxicity and complex diabetogenic effects.

Type II diabetes mellitus (T2DM) is characterized by insulin resistance, β-cell dysfunction and hyperglycemia. In addition to well known risk factors such as lifestyle and genetic risk score, accumulation of environmental toxicants in organs relevant to glucose metabolism is increasingly recognized as additional risk factors for T2DM. Here, we describe the development of an in vivo oral cadmium (Cd) exposure model.

Cadmium-mediated pancreatic islet transcriptome changes in mice and cultured mouse islets.

Type II diabetes mellitus (T2DM) is a multifactorial disease process that is characterized by insulin resistance and impairment of insulin-producing pancreatic islets. There is evidence that environmental exposure to cadmium contributes to the development of T2DM. The presence of cadmium in human islets from the general population and the uptake of cadmium in β-cells have been reported.

Single well, single-common primer pair, dual probe, duplex qPCR assay for the quantification of mRNA splicing variants.

Quantifying the ratio of alternatively spliced mRNA variants of genes with known alternative splicing variants is highly relevant for many applications. Herein, we describe the validation of a quantitative PCR design for the simplified quantification of known mRNA splice variants. The assay uses a single-common primer pair, dual probe design for the determination of splicing variants in a single well configuration.

Pancreatic Islets Accumulate Cadmium in a Rodent Model of Cadmium-Induced Hyperglycemia.

Cadmium (Cd) is an anthropogenic as well as a naturally occurring toxicant associated with prediabetes and T2DM in humans and experimental models of Cd exposure. However, relatively few studies have examined the mechanism(s) of Cd-induced hyperglycemia. The purpose of this study was to examine the role of pancreatic islets in Cd-induced hyperglycemia.

Caring for Hospitalized Patients with Diabetes Mellitus, Hyperglycemia, and COVID-19: Bridging the Remaining Knowledge Gaps.

Purpose Of Review: This review discusses the interplay between coronavirus disease 2019 (COVID-19, caused by SARS-CoV-2 infection), diabetes mellitus, and hyperglycemia in the hospital setting. There are data emerging about diabetes and hyperglycemia, their prevalence, and potential risks in the setting of SARS-CoV-2 infection and COVID-19.

Recent Findings: It is known that viral infections exert effects on beta cell function and insulin resistance.

Exploring the Association Between Demographics, SLC30A8 Genotype, and Human Islet Content of Zinc, Cadmium, Copper, Iron, Manganese and Nickel.

A widely prevalent single nucleotide polymorphism, rs13266634 in the SLC30A8 gene encoding the zinc transporter ZnT8, is associated with an increased risk for T2DM. ZnT8 is mostly expressed in pancreatic insulin-producing islets of Langerhans. The effect of this variant on the divalent metal profile in human islets is unknown.

Imaging trace element distributions in single organelles and subcellular features.

The distributions of chemical elements within cells are of prime importance in a wide range of basic and applied biochemical research. An example is the role of the subcellular Zn distribution in Zn homeostasis in insulin producing pancreatic beta cells and the development of type 2 diabetes mellitus. We combined transmission electron microscopy with micro- and nano-synchrotron X-ray fluorescence to image unequivocally for the first time, to the best of our knowledge, the natural elemental distributions, including those of trace elements, in single organelles and other subcellular features.

Association between urinary cadmium levels and prediabetes in the NHANES 2005-2010 population.

Evidence suggests an association between exposure to cadmium and dysglycemia. To investigate this matter, we examined the relationship between urinary cadmium and prediabetes in the cross sectional National Health and Nutrition Examination Survey (NHANES). NHANES participants for the years 2005 through 2010 aged ≥ 40 years were included in the analysis.

Denosumab for management of parathyroid carcinoma-mediated hypercalcemia.

Context: Most of the morbidity and mortality from parathyroid cancer is due to PTH-mediated hypercalcemia. Classically, management mainly consists of surgical resection, chemotherapy, and alleviation of hypercalcemia using bisphosphonates and calcium receptor agonists. The use of denosumab in the treatment of parathyroid cancer-mediated hypercalcemia has not been reported.

Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures.

Brain carbonic anhydrases (CAs) are known to modulate neuronal signalling. Using a novel CA VII (Car7) knockout (KO) mouse as well as a CA II (Car2) KO and a CA II/VII double KO, we show that mature hippocampal pyramidal neurons are endowed with two cytosolic isoforms. CA VII is predominantly expressed by neurons starting around postnatal day 10 (P10).

Accumulation of cadmium in insulin-producing β cells.

Evidence suggests that chronic low level cadmium exposure impairs the function of insulin-producing β cells and may be associated with type-2 diabetes mellitus. Herein, we describe the cadmium content in primary human islets and define the uptake kinetics and effects of environmentally relevant cadmium concentrations in cultured β cells. The average cadmium content in islets from 10 non-diabetic human subjects was 29 ± 7 nmol/g protein (range 7 to 72 nmol/g protein).

Acute cytokine-mediated downregulation of the zinc transporter ZnT8 alters pancreatic beta-cell function.

Genetic studies suggest that Zn transporters such as ZnT8 play a role in insulin secretion by pancreatic beta-cells; however, little is known about the dynamic roles of Zn trafficking pathways on beta-cell physiology. To test the acute effects of the inflammatory cytokines interleukin 1 beta (IL1 beta) and tumor necrosis factor alpha (TNFalpha) on Zn homeostasis, the mRNA expression profile of Zn transporters of the ZnT and ZIP families was examined. Exposure of MIN6 cells or primary murine islets to IL1 beta or TNFalpha altered the mRNA expression profile of Zn transporters; most notable was decreased ZnT8 mRNA levels.

1,25-Dihydroxyvitamin D-mediated hypercalcemia in oleogranulomatous mastitis (paraffinoma), ameliorated by glucocorticoid administration.

Objective: To report a case of oleogranulomatous mastitis (paraffinoma) in which both the hypercalcemia and the inappropriately elevated 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were successfully reduced by administration of prednisone.

Methods: We describe the clinical, imaging, and laboratory findings in the study patient. Furthermore, we review the relevant literature regarding hypercalcemia in oleogranulomatous mastitis.

AT1 and AT2-receptor antagonists inhibit Ang II-mediated facilitation of noradrenaline release in human atria.

It is generally accepted that regulation of blood pressure and sympathetic neurotransmission by angiotensin (Ang) II is brought about through activation of AT1-receptors. Since recent studies demonstrated a high proportion of AT2-receptors in the human heart, the aim of our study was to investigate whether Ang II modulates noradrenaline release also through activation of AT2-receptors in this tissue. Human atrial appendages were prelabeled with [3H]-noradrenaline and electrically field-stimulated.