Adenosine kinase (EC 2.7.1.20) (AK) (Adenosine 5'-phosphotransferase)

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Deletion of pancreatic β-cell adenosine kinase improves glucose homeostasis in young mice and ameliorates streptozotocin-induced hyperglycaemia.

Severe reduction in the β-cell number (collectively known as the β-cell mass) contributes to the development of both type 1 and type 2 diabetes. Recent pharmacological studies have suggested that increased pancreatic β-cell proliferation could be due to specific inhibition of adenosine kinase (ADK). However, genetic evidence for the function of pancreatic β-cell ADK under physiological conditions or in a pathological context is still lacking. In this study, we crossed mice carrying LoxP-flanked Adk gene with Ins2-Cre mice to acquire pancreatic β -cell ADK deficiency (Ins2-Cre Adk ) mice. Our results revealed that Ins2-Cre Adk mice showed improved glucose metabolism and β-cell mass in younger mice, but showed normal activity in adult mice. Moreover, Ins2-Cre Adk mice were more resistant to streptozotocin (STZ) induced hyperglycaemia and pancreatic β-cell damage in adult mice. In conclusion, we found that ADK negatively regulates β-cell replication in young mice as well as under pathological conditions, such as STZ induced pancreatic β-cell damage. Our study provided genetic evidence that specific inhibition of pancreatic β-cell ADK has potential for anti-diabetic therapy.

MeSH Terms

  • Adenosine Kinase
  • Aging
  • Animals
  • Cell Count
  • Cell Proliferation
  • Gene Deletion
  • Glucose
  • Homeostasis
  • Hyperglycemia
  • Insulin-Secreting Cells
  • Mice, Knockout
  • Streptozocin
  • Time Factors

Keywords

  • adenosine kinase
  • diabetes
  • insulin
  • replication
  • β cell


Neonatal hepatic steatosis by disruption of the adenosine kinase gene.

Neonatal hepatic steatosis (OMIM 228100) is a fatal condition of unknown etiology characterized by a pale and yellow liver and early postnatal mortality. In the present study, a deficit in adenosine-dependent metabolism is proposed as a causative factor. Physiologically, adenosine is efficiently metabolized to AMP by adenosine kinase (ADK), an enzyme highly expressed in liver. ADK not only ensures normal adenine nucleotide levels but also is essential for maintaining S-adenosylmethionine-dependent transmethylation processes, where adenosine, an obligatory product, has to be constantly removed. Homozygous Adk(-/-) mutants developed normally during embryogenesis. However, within 4 days after birth they displayed microvesicular hepatic steatosis and died within 14 days with fatty liver. Adenine nucleotides were decreased and S-adenosylhomocysteine, a potent inhibitor of transmethylation reactions, was increased in the mutant liver. Thus, a deficiency in adenosine metabolism is identified as a powerful contributor to the development of neonatal hepatic steatosis, providing a model for the rapid development of postnatally lethal fatty liver.

MeSH Terms

  • Adenine Nucleotides
  • Adenosine Kinase
  • Animals
  • Animals, Newborn
  • Apnea
  • Body Temperature
  • Disease Models, Animal
  • Fatty Liver
  • Female
  • Gene Targeting
  • Liver
  • Longevity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • S-Adenosylhomocysteine


Knowledge about aging and Alzheimer's disease among baccalaureate nursing students.

Alzheimer's disease (AD) is a debilitating disease that poses many physical, social, psychological, and management problems for family and professional caregivers. Nursing students' ability to meet this challenge was measured using Palmore's (1988) Facts on Aging Quiz, Version 2 (FAQ2) and the Alzheimer's Disease Knowledge (ADK) Test developed by Dieckmann, Zarit, Zarit, and Gatz (1988). No significant difference in ADK Test scores was found for students who had previous personal or educational experiences with AD. However, older students, seniors, and those who reported knowing more about AD had significantly better scores on the ADK Test. Knowledge about AD was not found to be related to knowledge of aging, and subjects as a group were found to exhibit a negative bias toward the elderly as measured by Palmore's FAQ2.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Alzheimer Disease
  • Education, Nursing, Baccalaureate
  • Health Knowledge, Attitudes, Practice
  • Humans
  • Students, Nursing