Although therapeutic advances are transforming the management of diabetes and obesity, side effects remain a limitation. A new drug, presented in Nature, regulates energy expenditure and food intake, reducing weight and reversing diabetes in animals.
A drug intended to treat obesity or type 2 diabetes should ideally increase energy expenditure and decrease food intake. This is not the case for incretin mimetics (GLP-1 agonists and dipeptylpeptidase-4 inhibitors) which, although they have transformed the pharmacotherapy of these diseases, only affect food intake through an increase in satiety. Their success continues on a global scale with a market that continues to grow driven by a surge in cases of obesity and type 2 diabetes.
In the light of an online publication in Natureit seems that a new avenue is opening up in the treatment of obesity and type 2 diabetes, via the activation of neurokinin 2 receptors (NK2R), a mechanism which would reduce appetite and to increase energy expenditure. This perspective is not really new, but until now, any therapeutic desire came up against the particularities of its endogenous ligand, neurokinin A, in particular its short duration of action and its limited specificity with respect to its receptors.
The pharmacological solution was to develop selective analogues of this ligand, which also have a long duration of action: a profile which makes their therapeutic use in humans conceivable.
Experimental studies: promising results
As for the mouse, the experimental studies presented in the publication of Nature have produced encouraging, even promising, results, these neurokinin A agonists being able to trigger weight loss through an increase in energy expenditure and an anorexigenic effect independent of the leptin pathway.
The hyperinsulinemia-euglycemia clamp technique also reveals that involvement of the NK2R pathway acutely increases insulin sensitivity. In both obese and diabetic macaques, pharmacological activation of NK2R receptors induces a significant reduction in body weight, blood sugar and cholesterol levels, while reducing insulin resistance, without nausea, vomiting or diarrhea.
So many experimental results which arouse keen interest in the prospects offered in the treatment of obesity and type 2 diabetes. It is true that the NK2R pathway activated by tachykinins, including substance P and neurokinin A, has everything instead of playing a crucial role in the regulation of body weight by a dual action, both central and peripheral, due to the presence of myenteric neurons and receptors present in the colic muscles. This is the enteric nervous system, also known as the “second brain”, which maintains close relationships with the central nervous system.
Activation of the NK2R pathway actually leads to a whole series of cellular or enzymatic responses which will affect intestinal motility and central neurotransmission. It is part of the permanent dialogue between brain and digestive tract which seems disrupted during type 2 diabetes and obesity, via complex mechanisms partially revealed by the recent success of GLP-1 agonists.
The therapeutic interest of this new pharmacological class is obvious, but its development is, for the moment, at the embryonic stage. It is now appropriate to move from animal experimentation to evaluation in humans, which requires long-term work that is already on the agenda.
**Despite promising pre-clinical results, what potential challenges or unknowns remain in translating NK2R agonists into safe and effective therapies for humans?**
## Rethinking Diabetes and Obesity Treatment: An Interview
**Welcome to World Today News! Today, we’re discussing groundbreaking research on a potential new treatment for obesity and type 2 diabetes. Joining us are Dr. Emily Carter, a leading endocrinologist, and Dr. James Wilson, a pharmacologist specializing in metabolic disorders.**
**Dr. Carter and Dr. Wilson, thank you for joining us.**
**Dr. Carter & Dr. Wilson:** Thank you for having us.
**(Section 1: The Current Landscape)**
**Interviewer:** The article highlights the limitations of existing treatments for diabetes and obesity, even with the success of incretin mimetics. Dr. Carter, could you elaborate on these limitations and why a new approach is needed?
**Dr. Carter:** (discusses the effectiveness but limited scope of incretin mimetics, focusing only on appetite reduction and the need for treatments that also address energy expenditure)
**Interviewer:** Dr. Wilson, how significant is the discovery of neurokinin 2 receptors as a potential target for these conditions? What makes this pathway so promising?
**Dr. Wilson:** (addresses the dual mechanism of NK2R activation- appetite suppression and increased energy expenditure- and its potential advantages over current treatments)
**(Section 2: The Science Behind NK2R Activation)**
**Interviewer:** The article mentions the challenges in developing effective NK2R agonists. Dr. Wilson, can you shed light on these challenges and how the new analogues overcome them?
**Dr. Wilson:** (explains the issues with the endogenous ligand, neurokinin A, and the advancements made in designing selective and long-acting analogues)
**Interviewer:** Dr. Carter, based on the experimental results in mice and macaques, what are the most compelling aspects of NK2R activation for treating Type 2 Diabetes?
**Dr. Carter:** (highlights the weight loss, blood sugar regulation, cholesterol reduction, and improved insulin sensitivity observed in animal studies)
**(Section 3: Looking Ahead – Challenges and Possibilities)**
**Interviewer:** Dr. Wilson, what are the next steps in translating these promising findings into human therapies?
**Dr. Wilson:** (discusses the transition from animal models to clinical trials, emphasizing the need for long-term safety and efficacy evaluations)
**Interviewer:** Dr. Carter, what are your hopes and concerns regarding the potential impact of these new drugs on patients with obesity and type 2 diabetes?
**Dr. Carter:** ( expresses excitement about the potential for improved treatments but also cautions about potential side effects and the importance of personalized medicine)
**Interviewer:**
Thank you both for sharing your expertise and insights with us. This research holds great promise for those living with these challenging conditions.
**Dr. Carter & Dr. Wilson:** Thank you for having us.
**Concluding remarks from the Interviewer:** Stay tuned to World Today News for continued coverage of this exciting development in the fight against obesity and type 2 diabetes.
**End of Interview**
