Endocrinology and Metabolism

Review Article

Diabetes, obesity and metabolism
Intrarenal Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors on Tubuloglomerular Feedback and Natriuresis: Eun Sil Koh, Gheun-Ho Kim, Sungjin Chung; Endocrinol Metab. 2023;38(4):359-372. Published online July 24, 2023; DOI: https://doi.org/10.3803/EnM.2023.1764

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When sodium-glucose cotransporter-2 (SGLT2) inhibitors were first introduced a decade ago, no one expected them to have substantial effects beyond their known glucose-lowering effects, until the emergence of evidence of their robust renal and cardiovascular benefits showing that they could attenuate progression of kidney disease, irrespective of diabetes, as well as prevent the development of acute kidney injury. Still, the precise and elaborate mechanisms underlying the major organ protection of SGLT2 inhibitors remain unclear. SGLT2 inhibitors inhibit the reabsorption of sodium and glucose in the proximal tubule of the kidney and then recovers tubuloglomerular feedback, whereby SGLT2 inhibitors reduce glomerular hyperfiltration. This simple demonstration of their beneficial effects has perplexed experts in seeking more plausible and as yet undisclosed explanations for the whole effects of SGLT2 inhibitors, including metabolism reprogramming and the modulation of hypoxia, inflammation, and oxidative stress. Given that the renal benefits of SGLT2 inhibitors in patients with kidney disease but without diabetes were comparable to those seen in patients with diabetes, it may be reasonable to keep the emphasis on their hemodynamic actions. In this context, the aim of the present review is to provide a comprehensive overview of renal hemodynamics in individuals with diabetes who are treated with SGLT2 inhibitors, with a focus on natriuresis associated with the regulation of tubuloglomerular feedback and potential aquaresis. Throughout the discussion of alterations in renal sodium and water transports, particular attention will be given to the potential enhancement of adenosine and its receptors following SGLT2 inhibition.

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Original Article

Enhancement of Short-Term Memory by Methyl-6-(Phenylethynyl)-Pyridine in the BTBR T+tf/J Mouse Model of Autism Spectrum Disorder: Haijie Yang, Sung-Oh Huh, Jae Seung Hong; Endocrinol Metab. 2015;30(1):98-104. Published online March 27, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.1.98

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Abstract PDF PubReader

Background

Autism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors. This study evaluated the effect of methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, on memory enhancement in the BTBR T+tf/J (BTBR) mouse strain, which has been recognized as a model of ASD.

Methods

The pharmacological effects of MPEP on memory and motor coordination were assessed using the Morris water maze and rotarod tests in BTBR and C57BL/6J (B6) mice. Furthermore, we performed morphological analyses of cerebellar foliation in BTBR and B6 mice using hematoxylin and eosin staining.

Results

MPEP-treated BTBR mice exhibited improved learning and memory in the Morris water maze test. MPEP administration also improved motor coordination in the rotarod test. However, no significant difference was observed regarding the numbers of Purkinje cells in the cerebella of BTBR versus normal B6 mice.

Conclusion

This study suggests that the mGluR5 antagonist MPEP has the potential to ameliorate learning and memory dysfunction and impaired motor coordination in BTBR mice. These results further suggest that the BTBR mouse model may be useful in pharmacological studies investigating drugs that could potentially alleviate cognitive dysfunction in ASD.

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Postweaning Social Isolation and Autism-Like Phenotype: A Biochemical and Behavioral Comparative Analysis
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SSRN Electronic Journal .2021;[Epub] CrossRef
Abnormal Cerebellar Development Is Involved in Dystonia-Like Behaviors and Motor Dysfunction of Autistic BTBR Mice
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Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef
Common functional variants of the glutamatergic system in Autism spectrum disorder with high and low intellectual abilities
Andreas G. Chiocchetti, Afsheen Yousaf, Hannah S. Bour, Denise Haslinger, Regina Waltes, Eftichia Duketis, Tomas Jarczok, Michael Sachse, Monica Biscaldi, Franziska Degenhardt, Stefan Herms, Sven Cichon, Jörg Ackermann, Ina Koch, Sabine M. Klauck, Christi
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Targeting mGlu5 Metabotropic Glutamate Receptors in the Treatment of Cognitive Dysfunction in a Mouse Model of Phenylketonuria
Francesca Nardecchia, Rosamaria Orlando, Luisa Iacovelli, Marco Colamartino, Elena Fiori, Vincenzo Leuzzi, Sonia Piccinin, Robert Nistico, Stefano Puglisi-Allegra, Luisa Di Menna, Giuseppe Battaglia, Ferdinando Nicoletti, Tiziana Pascucci
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Case Report

A Case of Langerhans Cell Histiocytosis Presented with Central Diabetes Insipidus.: Byung Chul Kim, Mi Yeoun Lee, Young Kue Kim, Ok Jun Lee, Sung Soo Koong, Tae Keun Oh; J Korean Endocr Soc. 2005;20(5):513-518. Published online October 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.5.513

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Abstract PDF

Langerhans cell histiocytosis can cause central diabetes insipidus. Here, a case of Langerhans cell histiocytosis invading the pituitary stalk was experienced. The patient was 15 years old boy, with complaint of polydipsia and polyuria. A water deprivation test was carried out, and the urine osmolarity was increased from 165 to 469 mosm/kg following an injection of AVP to confirm the diagnosis of central diabetes insipidus. A pituitary function stimulation test gave a normal response. A sellar MRI was performed, which showed a thickened pituitary stalk mass (about 5.7mm), with an increased size, 6.9 mm, on a second MRI 2 month later. A tissue biopsy was performed, which showed aggregates of histiocytes and inflammatory cells, with prominent eosinophils (H&E), and also revealed strong reactivity to anti-CD1a antibody on the immunohistochemistry. After confirmative tissue diagnosis, the patient received radiotherapy (900 cGy). The thickened mass of the pituitary stalk disappeared on the MRI following the radiotherapy. The patient was managed with DDAVP nasal spray, after which the polyuric symptoms were completely relieved.

Citations

Citations to this article as recorded by

Adult Multisystem Langerhans Cell Histiocytosis Presenting with Central Diabetes Insipidus Successfully Treated with Chemotherapy
Jung-Eun Choi, Hae Ri Lee, Jung Hun Ohn, Min Kyong Moon, Juri Park, Seong Jin Lee, Moon-Gi Choi, Hyung Joon Yoo, Jung Han Kim, Eun-Gyoung Hong
Endocrinology and Metabolism.2014; 29(3): 394. CrossRef
Clinical Characteristics of Langerhans Cell Histiocytosis with Hypothalamo-Pituitary Involvement
Eun Shil Hong, Jung Hun Ohn, Jung Hee Kim, Yul Hwang-Bo, Jin Joo Kim, Jung Hee Kwon, Jung Won Lee, Se Youn Choi, Eun Kyung Lee, Sun Wook Cho, Chan Soo Shin, Kyong Soo Park, Hak Chul Jang, Bo Youn Cho, Hong Kyu Lee, Choong Ho Shin, Sei Won Yang, Seong Yeon
Endocrinology and Metabolism.2011; 26(1): 38. CrossRef
A Case of Idiopathic Central Diabetes Insipidus together with Primary Empty Sella and Combined Pituitary Hormone Deficiency
Sun Young Ahn, Kyu Hwan Bae, Myung Hwan Kim, Ji Hyun Lee, Ho Sang Shon, Eui Dal Jung
Journal of Korean Endocrine Society.2007; 22(4): 272. CrossRef

Original Article

The Significance of Plasma ADH in Differential Diagnosis of Central Diabetes Insipidus.: Ho Jong Lee, In Myung Yang, Sun Kee Min, Jung Hyun Noh, Cheol Young Park, Seung Joon Oh, Deog Yoon Kim, Jung Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi; J Korean Endocr Soc. 2001;16(4-5):438-446. Published online October 1, 2001

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Abstract PDF: BACKGROUND
Although the water restriction test(WRT) has been used as a standard test for the differential diagnosis of diabetes insipidus(DI), the measurement of plasma ADH concentration is also known to be useful method for differential diagnosis. Recent studies have shown that some patients with idiopathic central DI(CDI) were found to have a lesion on follow-up imaging studies. There have been no report in Korea on plasma ADH measurement for the differential diagnosis of DI, nor on follow-up imaging study of the idiopathic CDI. METHODS: We retrospectively reviewed the clinical and laboratory findings of 26 patients(12 men, 14 women, age 9-65 years) with CDI, including pituitary MRI or CT scan, who had been diagnosed with WRT and had undergone plasma ADH concentration measurement. RESULTS: 1) Clinical features of the patients with complete CDI did not differ from those of patients with partial CDI. 2) Maximal urine osmolality of complete CDI and partial CDI were 168+/-69mOsm/kg and 431+/-141mOsm/kg, respectively, and the percentage increase in the urinary osmolality after ADH injection was 209+/-149% and 29+/-17%, respectively. 3) Among the 26 patients, 10 patients had their plasma ADH measured. Nine patients in this group were diagnosed as CDI by WRT and plasma ADH concentration of the 9 was compatible for CDI. The plasma ADH level was also inappropriately low in one patient who had been diagnosed with primary polydipsia by WRT, the patient was diagnosed as partial CDI. 4) The findings of follow-up MRI revealed isolated thickening of the pituitary stalk in two cases of idiopathic CDI diagnosed initially with MRI. CONCLUSION: This study suggests that the measurement of plasma ADH can ensure a better differential diagnosis between partial CDI and primary polydipsia, and that the patients with idiopathic CDI should be examined regularly with MRI brain scan, including the pituitary gland.

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