bims-glecem 2024-01-07 papers

Issue of 2024–01–07
four papers selected by
Dipsikha Biswas, Københavns Universitet

Asian J Surg. 2024 Jan 05. pii: S1015-9584(23)02091-2. [Epub ahead of print]

Type-VI glycogen storage disease with compound mutation of PYGL gene.

Keywords: GSD-VI; Glycogen storage disease; PYGL gene

DOI: https://doi.org/10.1016/j.asjsur.2023.12.127

Intern Med. 2024 Jan 02.

A Case Report of Diabetes in a Patient with Glycogen Storage Disease Type 1a.

Yoshinori Kanemaru, Norio Harada, Naoki Wada, Takuma Yasuda, Emi Okamura, Toshihito Fujii, Masahito Ogura, Nobuya Inagaki.

Glycogen storage disease type 1a (GSD-1a) is a rare congenital disease. Recently, life expectancy with GSD-1a has been improved by its early diagnosis and management. Complications of diabetes with GSD-1a are extremely rare. The optimal treatment for glucose control using this disease combination remains unclear. The existence of GSD-1a and diabetes can cause both hypoglycemia and hyperglycemia, making glucose control especially problematic. In the present report, α-glucosidase inhibitor (α-GI) and dipeptidyl peptidase-4 (DPP-4) inhibitors improved hyperglycemia without symptoms of hypoglycemia in a patient with diabetes and GSD-1a using intermittent continuous glucose monitoring (isCGM).

Keywords: diabetes; dipeptidyl peptidase-4 inhibitor; glycogen storage disease type 1a; hypoglycemia; intermittently scanned continuous glucose monitoring; α-glucosidase inhibitor

DOI: https://doi.org/10.2169/internalmedicine.2766-23

J Am Chem Soc. 2023 Dec 29.

Transient Structural Dynamics of Glycogen Phosphorylase from Nonequilibrium Hydrogen/Deuterium-Exchange Mass Spectrometry.

Monika Kish, Dylan P Ivory, Jonathan J Phillips.

It remains a major challenge to ascertain the specific structurally dynamic changes that underpin protein functional switching. There is a growing need in molecular biology and drug discovery to complement structural models with the ability to determine the dynamic structural changes that occur as these proteins are regulated and function. The archetypal allosteric enzyme glycogen phosphorylase is a clinical target of great interest to treat type II diabetes and metastatic cancers. Here, we developed a time-resolved nonequilibrium millisecond hydrogen/deuterium-exchange mass spectrometry (HDX-MS) approach capable of precisely locating dynamic structural changes during allosteric activation and inhibition of glycogen phosphorylase. We resolved obligate transient changes in the localized structure that are absent when directly comparing active/inactive states of the enzyme and show that they are common to allosteric activation by AMP and inhibition by caffeine, operating at different sites. This indicates that opposing allosteric regulation by inhibitor and activator ligands is mediated by pathways that intersect with a common structurally dynamic motif. This mass spectrometry approach uniquely stands to discover local transient structural dynamics and could be used broadly to identify features that influence the structural transitions of proteins.

DOI: https://doi.org/10.1021/jacs.3c08934

Med Sci Sports Exerc. 2023 Dec 27.

Low Energy Availability Followed by Optimal Energy Availability Does Not Benefit Performance in Trained Females.

Mikkel Oxfeldt, Daniel Marsi, Peter M Christensen, Ole Emil Andersen, Frank Ted Johansen, Maj Bangshaab, Jeyanthini Risikesan, Jan S Jeppesen, Ylva Hellsten, Stuart M Phillips, Anna K Melin, Niels Ørtenblad, Mette Hansen.

PURPOSE: Short periods of reduced energy availability are commonly undertaken by athletes to decrease body mass, possibly improve the power-to-mass ratio, and enhance physical performance. Our primary aim was to investigate the impact of 10 days of low energy availability (LEA) followed by 2 days of optimal energy availability (OEA) on physical performance parameters in trained females. Secondly, physiological markers at the whole-body and molecular level related to performance were evaluated.
METHODS: Thirty young trained eumenorrheic females were matched in pairs based on training history and randomized to a 10-day intervention period of LEA (25 kcal • fat-free mass (FFM)-1 • day-1) or OEA (50 kcal • FFM-1 • day-1) along with supervised exercise training. Before the intervention, participants underwent a 5-day run-in period with OEA + supervised exercise training. Following the LEA intervention, two days of recovery with OEA were completed. Participants underwent muscle biopsies, blood sampling, physical performance tests, body composition measurements, and resting metabolic rate measurements. A linear mixed model was used with group and time as fixed effects and subject as random effects.
RESULTS: Compared to OEA, LEA resulted in reduced body mass, muscle glycogen content, repeated sprint ability, 4-min time trial performance, and rate of force development of the knee extensors (absolute values) (p < 0.05). Two days of recovery restored 4-min time trial performance and partly restored repeated sprint ability, but performance remained inferior to the OEA group. When expressed relative to body mass, LEA did not enhance performance.
CONCLUSIONS: Ten days of LEA resulted in impaired performance (absolute values), with concomitant reductions in muscle glycogen. Two days of recovery with OEA partially restored these impairments, although physical performance (absolute values) was still inferior to being in OEA. Our findings do not support the thesis that LEA giving rise to small reductions in body mass improves the power-to-mass ratio and, thus, increases physical performance.

DOI: https://doi.org/10.1249/MSS.0000000000003370