bims-ciryme 2019-09-29 papers

Neurosci Res. 2019 Sep 24. pii: S0168-0102(19)30470-5. [Epub ahead of print]

The central circadian clock of the suprachiasmatic nucleus as an ensemble of multiple oscillatory neurons.

Circadian rhythms are oscillations with approximately 24-h period that appear in most of physiological events in our body. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the central circadian pacemaker in mammals and entrains to the environmental light/dark cycle. The SCN is a network structure composed of multiple types of γ-amino butyric acid (GABA)-ergic neurons and glial cells. Although individual SCN neurons have intracellular molecular machinery of circadian clock and the ability to oscillate cell-autonomously, interneuronal communications among these neurons are essential for the circadian pacemaking of the SCN. However, the mechanisms underlying the SCN network remain largely unknown. Here, I briefly review the molecular, cellular, and anatomical structures of the SCN and introduce recent studies aiming to understand the differential roles of multiple neuropeptides and neuropeptide-expressing neurons in the SCN network.

Keywords: Circadian rhythm; GABA; VIP; clock gene; neural network; suprachiasmatic nucleus; vasopressin

DOI: https://doi.org/10.1016/j.neures.2019.08.003

Diabetes Care. 2019 Sep 23. pii: dc191142. [Epub ahead of print]

Reduction in Glycated Hemoglobin and Daily Insulin Dose Alongside Circadian Clock Upregulation in Patients With Type 2 Diabetes Consuming a Three-Meal Diet: A Randomized Clinical Trial.

Daniela Jakubowicz, Zohar Landau, Shani Tsameret, Julio Wainstein, Itamar Raz, Bo Ahren, Nava Chapnik, Maayan Barnea, Tali Ganz, Miriam Menaged, Naomi Mor, Yosefa Bar-Dayan, Oren Froy.

OBJECTIVE: In type 2 diabetes, insulin resistance and progressive β-cell failure require treatment with high insulin doses, leading to weight gain. Our aim was to study whether a three-meal diet (3Mdiet) with a carbohydrate-rich breakfast may upregulate clock gene expression and, as a result, allow dose reduction of insulin, leading to weight loss and better glycemic control compared with an isocaloric six-meal diet (6Mdiet).
RESEARCH DESIGN AND METHODS: Twenty-eight volunteers with diabetes (BMI 32.4 ± 5.2 kg/m2 and HbA1c 8.1 ± 1.1% [64.5 ± 11.9 mmol/mol]) were randomly assigned to 3Mdiet or 6Mdiet. Body weight, glycemic control, continuous glucose monitoring (CGM), appetite, and clock gene expression were assessed at baseline, after 2 weeks, and after 12 weeks.
RESULTS: 3Mdiet, but not 6Mdiet, led to a significant weight loss (-5.4 ± 0.9 kg) (P < 0.01) and decreased HbA1c (-12 mmol/mol, -1.2%) (P < 0.0001) after 12 weeks. Fasting glucose and daily and nocturnal glucose levels were significantly lower on the 3Mdiet. CGM showed a significant decrease in the time spent in hyperglycemia only on the 3Mdiet. Total daily insulin dose was significantly reduced by 26 ± 7 units only on the 3Mdiet. There was a significant decrease in the hunger and cravings only in the 3Mdiet group. Clock genes exhibited oscillation, increased expression, and higher amplitude on the 3Mdiet compared with the 6Mdiet.
CONCLUSIONS: A 3Mdiet, in contrast to an isocaloric 6Mdiet, leads to weight loss, significant reduction in HbA1c, appetite, and overall glycemia, with a decrease in daily insulin. Upregulation of clock genes seen in this diet intervention could contribute to the improved glucose metabolism.

DOI: https://doi.org/10.2337/dc19-1142

J Mol Endocrinol. 2019 Sep 01. pii: JME-19-0153.R1. [Epub ahead of print]

Circadian Clock Genes and the Transcriptional Architecture of the Clock Mechanism.

Kimberly H Cox, Joseph Takahashi.

The mammalian circadian clock has evolved as an adaptation to the 24-hour light/dark cycle on earth. Maintaining cellular activities in synchrony with the activities of the organism (such as eating and sleeping) helps different tissue and organ systems coordinate and optimize their performance. The full extent of the mechanisms by which cells maintain the clock are still under investigation, but involve a core set of clock genes that regulate large networks of gene transcription both by direct transcriptional activation/repression as well as the recruitment of proteins that modify chromatin states more broadly.

DOI: https://doi.org/10.1530/JME-19-0153