Publications by authors named "Yohsuke Ohkubo"

4 Publications

  • Page 1 of 1

Repression of insulin gene transcription by indirect genomic signaling via the estrogen receptor in pancreatic beta cells.

In Vitro Cell Dev Biol Anim 2019 Apr 21;55(4):226-236. Epub 2019 Feb 21.

Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.

The mechanism whereby 17β-estradiol (E2) mediates insulin gene transcription has not been fully elucidated. In this study, exposure of hamster insulinoma (HIT-T15) cells to 5 × 10 to 1 × 10 M E2 led to a concentration-dependent decrease of insulin mRNA levels. Transient expression of the estrogen receptor (ER) in HIT-T15 cells revealed that estrogen receptor α (ERα) repressed transcription of the rat insulin II promoter in both ligand-dependent and ligand-independent manners. The N-terminal A/B domain of ERα was not required for either activity. However, the repression was absent with mutated ER lacking the DNA-binding domain. Moreover, introducing mutations in the D-box and P-box of the zinc finger of ER (C227S, C202L) also abolished the repression. Deletion of the insulin promoter region revealed that nucleotide positions - 238 to - 144 (relative to the transcriptional start site) were needed for ER repression of the rat insulin II gene. PDX1- and BETA2-binding sites were required for the repression, but an estrogen response element-like sequence or an AP1 site in the promoter was not involved. In conclusion, we found that estrogen repressed insulin mRNA expression in a beta cell line. In addition, the ER suppressed insulin gene transcription in a ligand-independent matter. These observations suggest ER may regulate insulin transcription by indirect genomic signaling.
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http://dx.doi.org/10.1007/s11626-019-00328-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443913PMC
April 2019

Loss of μ-crystallin causes PPARγ activation and obesity in high-fat diet-fed mice.

Biochem Biophys Res Commun 2019 01 10;508(3):914-920. Epub 2018 Dec 10.

Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, 390-8621, Japan.

The thyroid hormone-binding protein μ-crystallin (CRYM) mediates thyroid hormone action by sequestering triiodothyronine in the cytoplasm and regulating the intracellular concentration of thyroid hormone. As thyroid hormone action is closely associated with glycolipid metabolism, it has been proposed that CRYM may contribute to this process by reserving or releasing triiodothyronine in the cytoplasm. We aimed to clarify the relationship between CRYM and glycolipid metabolism by comparing wild-type and CRYM knockout mice fed a high-fat diet. Each group was provided a high-fat diet for 10 weeks, and then their body weight and fasting blood glucose levels were measured. Although no difference in body weight was observed between the two groups with normal diet, the treatment with a high-fat diet was found to induce obesity in the knockout mice. The knockout group displayed increased dietary intake, white adipose tissue, fat cell hypertrophy, and hyperglycemia in the intraperitoneal glucose tolerance test. In CRYM knockout mice, liver fat deposits were more pronounced than in the control group. Enhanced levels of PPARγ, which is known to cause fatty liver, and ACC1, which is a target gene for thyroid hormone and is involved in the fat synthesis, were also detected in the livers of CRYM knockout mice. These observations suggest that CRYM deficiency leads to obesity and lipogenesis, possibly in part through increasing the food intake of mice fed a high-fat diet.
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http://dx.doi.org/10.1016/j.bbrc.2018.12.038DOI Listing
January 2019

A somatotropin-producing pituitary adenoma with an isolated adrenocorticotropin-producing pituitary adenoma in a female patient with acromegaly, subclinical Cushing's disease and a left adrenal tumor.

Endocr J 2014 4;61(6):589-95. Epub 2014 Apr 4.

Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.

A 67-year-old female with hypertension and impaired glucose tolerance was admitted to our hospital because of a typical acromegalic appearance, including large, thickened bulky hands and feet, and a large prominent forehead and tongue. She did not have a Cushingoid appearance, such as a moon-face, buffalo hump, purple striae or central obesity. The laboratory data revealed a serum GH level of 4.6 ng/mL and serum insulin-like growth factor-1 level of 811 ng/mL. The oral glucose tolerance test showed no suppression of the GH values. An endocrine examination showed a lack of circadian rhythmicity of ACTH and cortisol. Cortisol was not suppressed by a low dose of dexamethasone during the suppression test, but was suppressed by a high dose of dexamethasone. A radiological study revealed two isolated adenomas in the pituitary and a left adrenal tumor. These findings strongly suggested a diagnosis of acromegaly with subclinical Cushing's disease and a left adrenal incidentaloma. Transsphenoidal surgery was performed. Hematoxylin and eosin staining showed that the left and right pituitary adenomas were composed of basophilic and acidophilic cells, respectively. Immunohistochemical staining showed the left adenoma to be positive for ACTH and negative for GH. In contrast, the right adenoma was GH-positive and ACTH-negative. This is a rare case of independent double pituitary adenomas with distinct hormonal features. We also provide a review of the previously reported cases of double pituitary adenomas and discuss the etiology of these tumors.
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http://dx.doi.org/10.1507/endocrj.ej14-0093DOI Listing
April 2015

Occurrence of IgG4-related hypophysitis lacking IgG4-bearing plasma cell infiltration during steroid therapy.

Intern Med 2014 1;53(7):753-7. Epub 2012 Mar 1.

Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Shinshu University School of Medicine, Japan.

Eight years after an episode of multiple IgG4-related disease, a pituitary mass with panhypopituitarism and a visual disturbance developed in a 70-year-old man under low-dose steroid therapy. A pituitary biopsy revealed findings of lymphocytic hypophysitis with the absence of IgG4-positive plasma cell infiltration. The serum IgG4 level was unremarkable. Although performing a pituitary biopsy and measuring the serum IgG4 level is crucial for making a diagnosis of IgG4-related hypophysitis, it is occasionally difficult to diagnose the disease in patients treated with steroid therapy, as observed in the present case. Based on a review of the diagnosis, conducting a careful assessment is required, especially in men and elderly patients thought to have solitary hypophysitis.
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http://dx.doi.org/10.2169/internalmedicine.53.0714DOI Listing
May 2015
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