Liver-specific overexpression of HKDC1 increases hepatocyte size and proliferative capacity.

A primary role of the liver is to regulate whole body glucose homeostasis. Glucokinase (GCK) is the main hexokinase (HK) expressed in hepatocytes and functions to phosphorylate the glucose that enters via GLUT transporters to become glucose-6-phosphate (G6P), which subsequently commits glucose to enter downstream anabolic and catabolic pathways. In the recent years, hexokinase domain-containing-1 (HKDC1), a novel 5th HK, has been characterized by our group and others.

A Case of Supplement-Induced Hepatitis.

Acute hepatitis is an uncommon sequela of herbal supplement use. Regardless, considering the hepatotoxic effects of natural supplements is important, especially in patients taking other medications or substances. We herein describe a case of acute steatohepatitis in a patient who chronically consumed high doses of ashwagandha and other herbal supplements in the context of alcohol use and a multi-medication regimen.

Optimized protocol to isolate primary mouse peritoneal macrophage metabolites.

Peritoneal macrophages (PMs) have been shown to have higher stability compared to other macrophage subtypes. However, obtaining enough PMs from a single mouse is often a limitation for metabolomics analysis. Here, we describe a protocol to isolate metabolites from a small number of mouse primary PMs for 13C-stable glucose tracing and metabolomics.

Hexokinase 1 cellular localization regulates the metabolic fate of glucose.

The product of hexokinase (HK) enzymes, glucose-6-phosphate, can be metabolized through glycolysis or directed to alternative metabolic routes, such as the pentose phosphate pathway (PPP) to generate anabolic intermediates. HK1 contains an N-terminal mitochondrial binding domain (MBD), but its physiologic significance remains unclear. To elucidate the effect of HK1 mitochondrial dissociation on cellular metabolism, we generated mice lacking the HK1 MBD (ΔE1HK1).

Hexokinase domain-containing protein-1 in metabolic diseases and beyond.

Glucose phosphorylation by hexokinases (HKs) traps glucose in cells and facilitates its usage in metabolic processes dependent on cellular needs. HK domain-containing protein-1 (HKDC1) is a recently discovered protein with wide expression containing HK activity, first noted through a genome-wide association study (GWAS) to be linked with gestational glucose homeostasis during pregnancy. Since then, HKDC1 has been observed to be expressed in many human tissues.

Hepatocyte-Specific Loss of PPARγ Protects Mice From NASH and Increases the Therapeutic Effects of Rosiglitazone in the Liver.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is commonly observed in patients with type 2 diabetes, and thiazolidinediones (TZD) are considered a potential therapy for NASH. Although TZD increase insulin sensitivity and partially reduce steatosis and alanine aminotransferase, the efficacy of TZD on resolving liver pathology is limited. In fact, TZD may activate peroxisome proliferator-activated receptor gamma (PPARγ) in hepatocytes and promote steatosis.

Hepatic HKDC1 Expression Contributes to Liver Metabolism.

Glucokinase (GCK) is the principal hexokinase (HK) in the liver, operating as a glucose sensor to regulate glucose metabolism and lipid homeostasis. Recently, we proposed HK domain-containing 1 (HKDC1) to be a fifth HK with expression in the liver. Here, we reveal HKDC1 to have low glucose-phosphorylating ability and demonstrate its association with the mitochondria in hepatocytes.

HKDC1 Is a Novel Hexokinase Involved in Whole-Body Glucose Use.

In a recent genome-wide association study, hexokinase domain-containing protein 1, or HKDC1, was found to be associated with gestational glucose levels during 2-hour glucose tolerance tests at 28 weeks of pregnancy. Because our understanding of the mediators of gestational glucose homeostasis is incomplete, we have generated the first transgenic mouse model to begin to understand the role of HKDC1 in whole-body glucose homeostasis. Interestingly, deletion of both HKDC1 alleles results in in utero embryonic lethality.

Mechanisms of acetylcholine-mediated vasodilation in systemic arteries from mourning doves (Zenaida macroura).

For mammals, acetylcholine (ACh) promotes endothelium-dependent vasodilation primarily through nitric oxide (NO) and prostaglandin-mediated pathways, with varying reliance on endothelial-derived hyperpolarizing factors. Currently, no studies have been conducted on small systemic arteries from wild birds. We hypothesized that ACh-mediated vasodilation of isolated small arteries from mourning doves (Zenaida macroura) would likewise depend on endothelial-derived factors.