Cells use a synchronized 'traffic control system' to determine nutrient availability and energy balance

BEER-SHEVA, Israel, September 2, 2025 – Scientists at Ben-Gurion University of the Negev have discovered that human cells operate a sophisticated, synchronized traffic control system that actively monitors nutrient availability and precisely controls cellular energy balance and blood sugar levels. This finding challenges long-held assumptions about how cells sense and respond to changing nutrient levels—and offers a promising new target for treating diabetes and cancer.

The study was led by Prof. Ehud Ohana and PhD student Noa Yehoshua and published recently in Nature Communications (https://doi.org/10.1038/s41467-025-62103-3). Prof. Ohana's lab is back up and running in an alternate location following its destruction by the Iranian missile strike on Soroka University Medical Center.

All cells must produce and use energy to live every single moment. Therefore, they face a constant challenge: how to quickly sense nutrient availability and maintain proper energy balance.

Until now, scientists believed cells primarily relied on relatively slow internal sensing mechanisms that could take hours to adjust metabolism.

However, this new study reveals an elegant mechanism: cells have evolved a fully synchronized rapid-response system that directly monitors nutrient availability at their surface. Two key transporter proteins—the liver citrate transporter (NaCT) and glucose transporters (Glut)— don't just carry these energy-providing nutrients into or out of cells. They work together in perfect coordination, continuously sensing nutrient levels and communicating with other cells to maintain energy balance and control blood sugar through synchronized nutrient uptake that adjusts within minutes.

"This research fundamentally changes how we think about cellular nutrition and energy balance. Rather than passive recipients of randomly available nutrients, cells actively monitor and negotiate their intake through sophisticated, synchronized molecular systems that directly control blood sugar, carboxylic acids and energy balance. We have developed molecules that target these synchronized functions which, remarkably, lowered blood glucose in mice. Therefore, we have in-hand new potential and robust tools to cure diabetes, cancer, and other metabolic disorders," says Prof. Ohana.

The Molecular Partnership

Think of NaCT and Glut as two synchronized traffic controllers in constant communication, continually coordinating to maintain optimal energy balance and nutrient control. The researchers identified a specific molecular region in NaCT called the H4c domain that enables this molecular coordination. When one transporter senses changes in nutrient availability, it immediately signals the other to adjust accordingly, ensuring perfect synchronization in energy management.

The coordination is remarkable: when liver cells are starved of glucose, both glucose and citrate uptake increase dramatically to maintain energy balance. However, the moment glucose becomes available again, elevated uptake stops.

Targeting the System: A Potential Breakthrough for Diabetes and Cancer

The therapeutic implications are promising. When researchers genetically disrupted NaCT expression in mice, something interesting happened: cells absorbed notably more glucose from their surroundings, and consequently, blood glucose levels dropped substantially.

By targeting this synchronized nutrient-sensing system, scientists can effectively control blood sugar levels in living animals. The approach suggests a potentially valuable treatment strategy: by strategically targeting NaCT, physicians might be able to help diabetic patients' cells pull more glucose from their bloodstream, effectively lowering blood sugar levels and potentially offering a new highly efficient therapeutic approach for diabetes.

Beyond Diabetes: Developing a Cure for Metabolic Diseases

The discovery extends beyond diabetes treatment toward potential cures for multiple metabolic diseases. Cancer cells notoriously hijack glucose transporters while suppressing NaCT—a combination that fuels their aggressive growth. Based on this, Prof. Ohana, in collaboration with Prof. Shimon Ben-Shabat, has engineered new molecular entities that reprogram tumor cell metabolism, which will be developed for clinical treatments in collaboration with Prof. Nicola Mabjeesh (head of Urology, Soroka University Medical Center) and Dr. Sabri El-Saied (Deputy head of Otolaryngology, Soroka University Medical Center). The team has shown that these new molecules eradicate specific tumors in mice. Therefore, understanding this synchronized NaCT-Glut system could unlock new ways to eradicate cancer cells while preserving healthy tissue. The study, by Ph.D. student Noa Yehoshua and Hadar Eini-Rider with key contributions from Ahlam Khamaysi, Aharon Keshet, and other team members, represents an important shift: from targeting individual proteins or cell signals to targeting the orchestrated function of transporter interactions — potentially leading to breakthrough treatments that could cure rather than just manage these challenging diseases.

"This scientific discovery is an example of cutting edge research which becomes an opportunity to develop new drugs. BGN Technologies, the tech transfer company of Ben-Gurion University, is committed to translating this achievement into collaborations with international companies to bring these discoveries "from lab bench to bedside" to affect millions worldwide," noted Dr. Galit Mazooz-Perlmuter, VP Business Development - Biopharma, Biotechnology and Medical Device.