著者

Nao Nomura Katsumi Iizuka Eiichi Goshima Kazuyoshi Hosomichi Atsushi Tajima Sodai Kubota Yanyan Liu Ken Takao Takehiro Kato Masami Mizuno Takuo Hirota Tetsuya Suwa Yukio Horikawa Daisuke Yabe

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ21-0526, (Released:2021-11-19)

被引用文献数

1

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Glucokinase has an important role in regulating glycolysis as a glucose sensor in liver and pancreatic β cells. Glucokinase-maturity onset diabetes in young (GCK-MODY also known as MODY2) is caused by autosomal dominant gene mutation of the GCK gene; it is characterized by mild fasting hyperglycemia and small 2-h glucose increment during 75 g-oral glucose tolerance test (OGTT) as well as near-normal postprandial glucose variabilities. A 10-year-old girl with family history of diabetes visited her physician after being found positive for urinary glucose by school medical checkup. She received a diagnosis of diabetes based on the laboratory data: 75 g-OGTT (mild fasting hyperglycemia and small 2-h glucose increment) and factory-calibrated glucose monitoring (mild elevation of average glucose level and near-normal glycemic variability), which raised suspicion of GCK-MODY. She was then referred to our institution for genetic examination, which revealed a GCK heterozygous mutation (NM_000162: exon10: c.1324G>T: p.E442X) in the proband as well as in her mother and maternal grandmother, who had been receiving anti-diabetes medications without knowing that they had GCK-MODY specifically. GCK-MODY cases show incidence of microvascular and macrovascular diseases similar to that of normal subjects, and their glucose levels are adequately controlled without anti-diabetes drug use. Thus, early and definitive diagnosis of MODY2 by genetic testing is important to avoid unnecessary medication.

著者

Kenta Nonomura Katsumi Iizuka Yayoi Kuwabara-Ohmura Daisuke Yabe

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

pp.4323-19, (Released:2020-03-19)

参考文献数

25

被引用文献数

4

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A 72-year-old man had type 2 diabetes (T2D) that had been diagnosed at 54 years old. Macroalbuminuria was first detected at age 64. While his HbA1c had been kept below 7%, his estimated glomerular filtration rate (eGFR) was declining rapidly. At 70 years old, his eGFR dropped below 50 ml/min/1.73 m2. A renal biopsy revealed diabetic nephropathy. sodium glucose transporter 2 inhibitors (SGLT2i)/glucagon-like peptide-1 receptor agonists (GLP-1RA) combination therapy substantially improved his eGFR and urinary albumin level, and the renoprotective effect persisted for the two-year study period. These findings suggest that SGLT2i and GLP-1RA can additively improve the renal function in patients with T2D.

著者

Katsumi IIZUKA Yukio HORIKAWA

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.55, no.4, pp.617-624, 2008 (Released:2008-08-27)

参考文献数

46

被引用文献数

62 158

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Excess carbohydrate intake leads to fat accumulation and insulin resistance. Glucose and insulin coordinately regulate de novo lipogenesis from glucose in the liver, and insulin activates several transcription factors including SREBP1c and LXR, while those activated by glucose remain unknown. Recently, a carbohydrate response element binding protein (ChREBP), which binds to the carbohydrate response element (ChoRE) in the promoter of rat liver type pyruvate kinase (LPK), has been identified. The target genes of ChREBP are involved in glycolysis, lipogenesis, and gluconeogenesis. Although the regulation of ChREBP remains unknown in detail, the transactivity of ChREBP is partly regulated by a phosphorylation/dephosphorylation mechanism. During fasting, protein kinase A and AMP-activated protein kinase phosphorylate ChREBP and inactivate its transactivity. During feeding, xylulose-5-phosphate in the hexose monophosphate pathway activates protein phosphatase 2A, which dephosphorylates ChREBP and activates its transactivity. ChREBP controls 50% of hepatic lipogenesis by regulating glycolytic and lipogenic gene expression. In ChREBP -/- mice, liver triglyceride content is decreased and liver glycogen content is increased compared to wild-type mice. These results indicate that ChREBP can regulate metabolic gene expression to convert excess carbohydrate into triglyceride rather than glycogen. Furthermore, complete inhibition of ChREBP in ob/ob mice reduces the effects of the metabolic syndrome such as obesity, fatty liver, and glucose intolerance. Thus, further clarification of the physiological role of ChREBP may be useful in developing treatments for the metabolic syndrome.