Impaired insulin secretion from the pancreatic islets of hypothyroidal growth-retarded mice.
The growth-retarded (grt) mouse shows thyroid dysfunction-related hyporesponsiveness to TSH. Thyroid hormone is a critical regulator of metabolism in many cells; thus, derangement of thyroid function affects many organs and systems. Experiments were conducted focusing on the function of the pancreatic islets in grt mice. We showed occurrence of a fasting hyperglycemia and a decreased plasma insulin level response to a glucose load in grt mice, despite normal insulin molecules being stored in secretory granules of pancreatic islets. We also demonstrated a reduction of insulin secretion in response to glucose administration from islets of grt mice in vitro, while the insulin release in response to KCl stimulation was comparable to that in normal mice, indicating that the isolated islets from grt mice have normal ATP-sensitive K(+) channels and postchannel activity. The mRNA expression levels of glucose transporter 2 and glucokinase in the islets of grt mice were similar to those in normal mice. Triiodothyronine administration to grt mice improved insulin secretion very slightly. On the other hand, mRNA for tyrosylprotein sulfotransferase 2 (Tpst2) was found to be expressed in the pancreatic islets of grt mice. Considering that Tpst2 is the responsible gene of grt mice, mutation of which is associated with a poor function of TSH receptor, the findings raise a possibility of involvement of factors including Tpst2 in the insulin hyposecretion in grt mice.
Taguchi
Yusuke
Y
Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan.
Tasaki
Yoshie
Y
Terakado
Kiyoshi
K
Kobayashi
Kenichi
K
Machida
Takeo
T
Kobayashi
Tetsuya
T
D000818:Animals; D012634:Bodily Secretions / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D006130:Growth Disorders / Q000209:etiology / Q000378:metabolism*; D007037:Hypothyroidism / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016253:Microscopy, Immunoelectron; D016133:Polymerase Chain Reaction; D011189:Potassium Chloride / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000008:administration & dosage / Q000494:pharmacology
D051273:Glucose Transporter Type 2; D007328:Insulin; D012333:RNA, Messenger; C495682:Slc2a2 protein, mouse; D014284:Triiodothyronine; D011189:Potassium Chloride; D015238:Sulfotransferases; C529648:TPST2 protein, mouse; C039079:protein-tyrosine sulfotransferase; D005947:Glucose