Increased expression of adenylyl cyclase isoforms in the adrenal gland of diabetic Goto-Kakizaki rat.
The spontaneously diabetic Goto-Kakizaki rat harbors the same defects expressed in human type 2 diabetes. It is not clear, however, whether stress factors emanating from the adrenal glands are involved in causing the diabetic state. For that reason, the authors studied gland size and expression of adenylyl cyclase isoforms in adrenal glands from Goto-Kakizaki and normal rats. Goto-Kakizaki rat adrenals were found to weigh only about half as much as those of control rats. This decrease was the result of a reduction of the cortex, especially of the zona fasciculata, whereas the medulla was unaffected. Cell density measurements showed that the total number of medullary cells in Goto-Kakizaki rats was lower than that in controls. In the cortex, the cell density did not differ between the two groups; thus, our results point to a marked hypotrophy. In the medulla of Goto-Kakizaki rats, the nuclear size was significantly increased, and there was also an overexpression of adenylyl cyclase 1, 2, 4, 6, and 8 isoforms in the adrenalin-producing cells, indicating an increased functional capacity. In the cortex, despite the cortical hypotrophy, adenylyl cyclase 5 immunoreactivity was markedly increased in Goto-Kakizaki rats, especially in the zona reticularis. It is unclear whether this morphologic change in the diabetic adrenal glands together with the overexpression of different adenylyl cyclase isoforms plays a role in the pathogenesis of this diabetic state or is a genetic defect or compensatory mechanism of diabetes in this spontaneous rodent model of type 2 diabetes.
Portela-Gomes
Guida Maria
GM
Gastroenterology Center and Center of Nutrition, Lisbon University, Lisbon, Portugal,
Grimelius
Lars
L
Johansson
Henry
H
Efendic
Suad
S
Wester
Kenneth
K
Abdel-Halim
Samy M
SM
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000302:Adrenal Cortex / Q000201:enzymology / Q000473:pathology; D000311:Adrenal Glands / Q000201:enzymology* / Q000473:pathology; D000313:Adrenal Medulla / Q000201:enzymology / Q000473:pathology; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009929:Organ Size; D051381:Rats; D014018:Tissue Distribution
D007527:Isoenzymes; D000262:Adenylyl Cyclases