Search PubMed⌕ Search

Biomedical subjects

S R Wagle

Publications and source records attributed to S R Wagle.

60 records · Page 4Linked to original sources
PubMedDate not supplied

Studies of hormonal regulation of metabolism using isolated hepatocytes.

A number of enzymatic methods have been developed to prepare hepatocytes using collagenase and hyaluronidase. However, best cell preparations are obtained by using only low concentrations of collagenase and exposing the liver to the enzyme for a very short period of time. These isolated cells with intact cell membranes and large numbers of microvilli on the cell surface respond to hormones at physiological concentrations suggesting that these microvilli contain hormone receptors. In addition, high glycogen content is essential to maintain the in vivo metabolic characteristics of the hepatocytes suggesting that intracellular glycogen plays an important role in the hormonal regulation of metabolism in hepatocytes. Studies with glucagon and insulin on carbohydrate metabolism show that the molar ratios of these hormones control gluconeogenesis and glycogenolysis. Furthermore, in vitro addition of insulin stimulates glycogen synthesis and activates glycogen synthase. Insulin also stimulates protein synthesis in cells containing high glycogen and maintains more normal parallel strands of polyribosomes. Studies with isolated hepatocytes from diabetic, hypophysectomized and adrenalectomized animals show a reduced glucagon response to glycogenolysis. This lack of glucagon response was not due to reduction in glycogen levels. Other hormones such as somatostatin and parathyroid also give rise to alterations in carbohydrate metabolism in isolated hepatocytes.

Adrenal Glands↗
PubMedDate not supplied

Studies on gluconeogenesis and stimulation of glycogen and protein synthesis in isolated hepatocytes in alloxan diabetic, normal fed and fasted animals.

Hepatocytes were isolated by collagenase in vitro perfusion technique. Net glucose production in isolated hepatocytes obtained from fed, fasted and alloxan diabetic rats was studied. Net glucose production from alanine, pyruvate and fructose was increased by 2-5 fold in isolated hepatocytes obtained from fasted and alloxan diabetic rats. Similar increases in the incorporation of 14C-bicarbonate into glucose was also observed. Net glucose production in isolated hepatocytes was also compared to other in vitro preparations. Net glucose production was much higher (2-5 fold) in isolated hepatocytes than that reported previously for liver slices or perfused liver. Studies on glycogen and protein synthesis show a 2 fold stimulation in the incorporation of 1-14C-glucoase into glycogen and U-14C-leucine into protein by the addition of 100 muU of insulin to isolated hepatocytes.

Animals↗
PubMedDate not supplied

The metabolism of drugs in isolated rat hepatocytes. A comparison with in vivo drug metabolism and drug metabolism in subcellular liver fractions.

The metabolism of drugs in isolated rat hepatocytes has been investigated. Drugs which are metabolized by aromatic hydrolation, aliphatic hydroylation, N-demethylation, or glucuronidation have been used as substrates. With some substrates the rate of metabolism in isolated hepatocytes compares with that in hepatic 900g supernatant fraction or microsomes, but other substrates are metabolized at a slower rate in isolated hepatocytes. For example, the rate of butamoxane hydroxylation in isolated hepatocytes is slower than that in microsomes. However, the rate of hydroxylation is hepatocytes is identical to that in perfused liver. The metabolism of drugs in isolated hepatocytes correlates with in vivo drug metabolism better than does metabolism in the hepatic 9000g supernatant fraction or microsomes.

Animals↗