New Therapeutic Targets for Type 2 Diabetes: How Metformin and GDF15 Fight High Blood Sugar

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Metformin Secrets: New Targets for Type 2 Diabetes

New Therapeutic Targets for Type 2 Diabetes: How Metformin and GDF15 Fight High Blood Sugar

Discover the latest breakthroughs in type 2 diabetes treatment, including metformin’s unknown mechanisms, hepatic gluconeogenesis regulation, and emerging therapeutic targets like GDF15 and TGF-β to improve glycaemic control.

New therapeutic targets for type 2 diabetes: Insights into metformin and hepatic gluconeogenesis
Date: June 7, 2024
Type 2 diabetes mellitus (T2DM) is one of the most challenging chronic diseases of the 21st century. Fasting blood sugar, or high glucose levels during fasting, is the most significant complication. Controlling it is difficult because insulin resistance leads to excessive glucose production in the liver, a process known as hepatic gluconeogenesis. This process is not yet fully scientifically understood.
Type 2 Diabetes and Hepatic Gluconeogenesis: Unlocking Metformin’s Complex Mechanisms
A recent review published by researchers from the University of Barcelona in the journal "Trends in Endocrinology & Metabolism" explores new therapeutic targets for type 2 diabetes and the complex actions of the most commonly used drug, "metformin".
Type 2 Diabetes Mellitus: Metformin’s Role, Fasting Blood Sugar, and New Therapeutic Targets
What is hepatic gluconeogenesis and why is it important in type 2 diabetes?

Hepatic gluconeogenesis is the process by which the liver produces glucose as needed. It provides the body with essential energy, especially during fasting or prolonged periods of food inactivity.
  • This process becomes overactive in patients with type 2 diabetes. This results in high blood sugar levels, leading to poor glycemic control, organ damage, and an increased risk of heart disease.
  • According to Professor Manuel Vazquez-Carra, "Some new factors, such as Growth Differentiation Factor 15 (GDF15), can reduce the amount of proteins that promote glucose production in the liver. This is an important discovery in the treatment of type 2 diabetes."
  • Other important pathways include TGF-β, which plays a key role in Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD). MASLD is common in patients with type 2 diabetes and can exacerbate liver health complications. Controlling these pathways can lead to better blood sugar control.
New Hope for Type 2 Diabetes: Targeting GDF15 to Stop Excessive Liver Glucose Production
Emerging Therapeutic Targets for Type 2 Diabetes
  • Recent research has found that targeting just one factor is not enough. Instead, combination therapies that control multiple pathways—such as TGF-β, TOX3, and TOX4—may yield better results.
  • Vazquez-Carra explains, “Controlling hepatic gluconeogenesis is challenging because it is essential for maintaining glucose during fasting and is regulated by multiple factors.”
  • During the COVID-19 pandemic, it was also observed that the SARS-CoV-2 virus increases the activity of proteins involved in gluconeogenesis in patients, leading to the common occurrence of hyperglycemia. This suggests that controlling glucose production in the liver is not limited to type 2 diabetes but is also important in other health conditions.

Metformin: Secrets of the Most CommonlUsed Antidiabetic Drug
  • Metformin is the most well-known drug for the treatment of type 2 diabetes. It primarily works by reducing glucose production in the liver. However, recent research has shown that its effects are not limited to AMPK activation.
  • Metformin also inhibits mitochondrial complex IV, thereby reducing the substrates needed for glucose production. Furthermore, it also affects the gut and increases GLP-1 secretion, which helps inhibit gluconeogenesis.
  • Vazquez-Carra says, “These discoveries open the way to developing next-generation anti-diabetic drugs that target both the gut and the liver. This could improve patients' blood sugar control and reduce drug side effects.”
Metformin: Secrets of the Most Commonly Used Antidiabetic Drug

GDF15 and New Possibilities
  • GDF15 is a new therapeutic target. Researchers are trying to develop GDF15-based therapies to improve glycemic control. This could reduce glucose production in the liver and provide other beneficial effects in the body.
  • Work in this direction also opens up the possibility of customized treatments and personalized medicine. This could allow patients to receive medication tailored to their body's needs, which was previously not possible.
GDF15 and New Possibilities
Importance of Nutrition and Lifestyle in Type 2 Diabetes
Lifestyle and nutrition are as important as medication in type 2 diabetes.
  • A balanced diet: High-fiber grains, vegetables, and fruits help control blood sugar.
  • Regular exercise: Daily walking, yoga, or light exercise improves insulin sensitivity.
  • Weight control: Excess weight can increase gluconeogenesis, so weight loss is important.
  • Stress management: Stress hormones can affect glucose production.
  • These measures increase medication effectiveness and improve blood sugar control.
Importance of Nutrition and Lifestyle in Type 2 Diabetes
COVID-19 and Type 2 Diabetes
The COVID-19 pandemic has presented new challenges for type 2 diabetes. The SARS-CoV-2 virus can cause hyperglycemia by increasing hepatic gluconeogenesis. This means that blood sugar levels in diabetic patients may rise rapidly during viral infection, increasing the risk of complications.
COVID-19 and Type 2 Diabetes
This makes it clear that future treatments will need to take into account the effects of infection and immune response.

Future Directions: Research and New Drugs
Further research aims to:
  • Develop GDF15-enhancing drugs
  • Develop next-generation anti-diabetic drugs
  • Promote customized treatment and personalized medicine
  • Combine lifestyle and nutritional interventions with medication
Future Directions: Research and New Drugs
These efforts can improve the treatment of type 2 diabetes and improve the quality of life of patients.

FAQs

1. What is Type 2 Diabetes?
Answer:
Type 2 diabetes is a chronic disease in which the body cannot use enough insulin or its production decreases. This results in high blood sugar. It is the most common type of diabetes and is most common in adults.

2. What are the symptoms of Type 2 Diabetes?
Answer:
Key symptoms include:
  • Frequent urination
  • Increased thirst
  • Frequent hunger
  • Fatigue and weakness
  • Blurred vision
  • Sudden weight changes
Sometimes symptoms are not apparent in the early stages, so regular blood sugar checks are essential.
3. What are the causes of type 2 diabetes?
Answer:
The main causes of type 2 diabetes are:
  • Insulin resistance:The body's cells are unable to use insulin properly.
  • Uncontrolled eating** and excessive sugar intake.
  • "Obesity" and lack of physical activity.
  • Genetics
  • Aging
 4. What is metformin?
Answer:
Metformin is the most commonly used anti-diabetic drug. It reduces glucose production in the liver and helps control blood sugar. Metformin also affects the gut and increases GLP-1 secretion, further improving glucose control.


 5. How is type 2 diabetes treated?

Answer:
Treatment includes:
  • Medication: metformin, acetaminophen, and other newer medications
  • Healthy diet:high-fiber grains, fruits, and vegetables
  • Regular exercise: walking, yoga, strength training
  • Weight control
  • Lifestyle modifications:reducing stress and getting enough sleep

6. What is GDF15 and what is its role in type 2 diabetes?
Answer:
GDF15 is a new therapeutic target. It reduces glucose production in the liver and helps control blood sugar. In the future, GDF15-based drugs may prove effective for type 2 diabetes.
7. What is the importance of lifestyle and diet in type 2 diabetes?
Answer:
Lifestyle and dietary control are very important in controlling blood sugar:
  • Balanced diet: fruits, vegetables, high fiber
  • Regular exercise: 30 minutes of walking or light exercise daily
  • Weight control
  • Stress management
  • Sleep management
8. What is the impact of COVID-19 on type 2 diabetes?
Answer:
The SARS-CoV-2 virus in COVID-19 can increase hepatic gluconeogenesis, leading to a rapid increase in blood sugar. Therefore, patients with diabetes should be especially careful during COVID-19.

9. What are future medications and research for type 2 diabetes?

Answer:
Future research is focused on the following areas:
  • GDF15-based therapies
  • Next-generation anti-diabetic drugs
  • Personalized treatment
  • Combination of lifestyle and medication
10. Can type 2 diabetes be completely cured?
Answer:
Complete treatment is difficult, but it can be controlled with medication, lifestyle modifications, and regular blood sugar monitoring. This can also prevent complications.
11. What role does gluconeogenesis play in type 2 diabetes?
Answer:
Gluconeogenesis is the process by which the liver produces glucose during fasting. In type 2 diabetes, this process becomes overactive, leading to increased blood sugar.
12. What are the side effects of metformin?
Answer:
Most people find metformin safe, but side effects can sometimes occur:
  • Abdominal pain or indigestion
  • Diarrhea or constipation
  • In rare cases, lactic acidosis
 13. Why is exercise important in type 2 diabetes?
Answer:
Exercise "increases insulin sensitivity", helps glucose enter cells, and promotes weight loss.
14. What is the importance of weight control in type 2 diabetes?
Answer:
Excess weight increases insulin resistance. Weight loss improves glucose control and may reduce the need for medication.
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Location: United States

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