GLP-1 (Gila Lizard Poison)

In the medical field there is an unspoken rule “Never question the doctor” after all they are highly intelligent & infallible. We have all been conditioned to follow them as though they are clergy of the white coat cult. But the fact that we give them so much credit & respect is what they depend on when regurgitating the gospel according to Big Pharma. That’s right they baffle us with their Latin based scientific terms that they have been taught to repeat from the package insert of the drugs they push. Here is my take on the latest craze, GLP-1.

The Gila monster, a venomous lizard native to the southwestern United States and northern Mexico, has played a significant role in the development of GLP-1 (glucagon-like peptide-1) based medications. Researchers discovered that the Gila monster’s venom contains a hormone called exendin-4, which mimics the effects of GLP-1 but is much more stable in the human body. This discovery led to the development of GLP-1 receptor agonists, such as exenatide (marketed as Byetta), which is used to manage type 2 diabetes.
GLP-1 is a hormone that increases insulin production and makes individuals feel satiated, but it has a very short half-life in the body, making it ineffective for long-term use. Exendin-4, found in Gila monster venom, has a longer half-life, allowing it to remain active in the body for a longer period. This property made it an ideal candidate for developing medications that could effectively regulate blood sugar levels and reduce appetite.
The development of GLP-1 receptor agonists, such as semaglutide (Ozempic and Wegovy), was directly influenced by the discovery of exendin-4 in Gila monster venom. These medications have become popular for treating obesity and type 2 diabetes, with semaglutide being particularly effective in reducing appetite and promoting weight loss.
In addition to its role in diabetes treatment, the Gila monster’s venom has also been studied for its potential in other medical applications. For example, exendin-4 has been shown to have a prolonged duration of action, making it a valuable component in the development of long-acting GLP-1 agonists.
The discovery of exendin-4 in Gila monster venom highlights the importance of studying natural sources for potential medical breakthroughs. This unique lizard’s venom has contributed significantly to the advancement of diabetes and obesity treatments, demonstrating the potential of nature to provide solutions to complex health issues.

Gila Monster Venom
Gila monster venom contains components that can paralyze prey, with some peptides in the venom acting similarly to the vasoactive intestinal peptide (VIP), which can cause paralysis in animals. The venom’s effects include the paralysis of prey, which is facilitated by the venom’s ability to disrupt normal physiological functions. Additionally, the venom can cause severe pain and other systemic effects in humans, although no human deaths have been reported from Gila monster bites. However, there have been rare cases where the venom has led to life-threatening conditions, such as angioedema, significant fluid losses, and atrioventricular conduction disorders. Despite these effects, there is currently no antivenom available for Gila monster bites.

Gila Monster Venom Paralysis
The Gila monster’s venom is known to cause paralysis, among other effects. The venom contains several neurotoxic components, including helothermine, which can lead to partial paralysis of the limbs and hypothermia in rats. Additionally, studies have shown that the venom can inhibit ion flux and block the electrical stimulation of skeletal muscles, leading to flaccid paralysis. These effects are consistent with the clinical symptoms observed in human victims, which may include paralysis and tachycardia. While the venom is not typically fatal to humans, it can cause significant neurological impairment.

Gila Monster Venom Paralysis
The Gila monster’s venom contains bioactive peptides that can cause paralysis of smooth muscle. These effects are attributed to the venom’s ability to interact with voltage-gated ion channels, particularly sodium (NaV) and calcium (CaV) channels, which play a crucial role in muscle function. For instance, Heloderma suspectum venom has been shown to bind to the S3–S4 loop within voltage-sensing domain IV of the skeletal muscle channel subtype, NaV1.4, leading to the inhibition of channel fast inactivation and altering Na+ influx, which can result in flaccid paralysis. Similarly, the venom also binds to voltage-sensing domain IV of the cardiac smooth muscle calcium channel, CaV1.2, which may contribute to tachycardia and other neuromuscular effects. These findings highlight the neurotoxic potential of Gila monster venom, which can affect both skeletal and smooth muscle tissues.

Gastrointestinal Smooth Muscle
The gastrointestinal (GI) tract relies heavily on smooth muscle for its motility and function. The smooth muscle in the GI tract is organized into two layers—circular and longitudinal—allowing for coordinated contractions that facilitate the movement of food, water, and waste through the tubular chambers of the digestive system. Unlike skeletal muscle, which is found in the proximal two-thirds of the esophagus and the external anal sphincter, the rest of the GI tract’s muscular layers consist of smooth muscle cells (SMCs).

Smooth muscle contractions in the GI tract are autonomous, meaning they can generate spontaneous electrical activity, such as slow waves, which are intrinsic to the muscle and not dependent on nervous input. These slow waves are initiated by interstitial cells of Cajal (ICC), which act as pacemakers and are electrically coupled to SMCs. The slow waves set the basic rhythm for contractions, but actual muscle contractions occur when spike potentials—true action potentials—are generated on the crests of these slow waves.
The contractions of smooth muscle in the GI tract are regulated by multiple factors, including enteric motor neurons, hormones, paracrine substances, and inflammatory mediators. These regulatory elements interact with SMCs, ICC, and PDGFRα+ cells, forming a syncytium that facilitates coordinated contractions. The enteric nervous system (ENS) plays a crucial role in modulating these contractions, while the autonomic nervous system (ANS) influences them indirectly through the ENS.

Smooth muscle in the GI tract exhibits both phasic and tonic contractions. Phasic contractions are rapid and rhythmic, occurring in the small intestine and posterior stomach, while tonic contractions are sustained and occur in sphincters and the anterior stomach. This variability in contractile properties allows the GI tract to perform both mixing and propulsive functions, such as segmentation and peristalsis.
The smooth muscle in the GI tract is also capable of maintaining a muscle tone, which helps prevent “flabbiness” in empty organs and allows for continuous expansion as they fill. This is particularly important in hollow organs like the stomach and urinary bladder. Additionally, the smooth muscle is organized into bundles, with the contractile apparatus spanning cell boundaries, enabling efficient mechanical function.

In summary, the smooth muscle of the GI tract is a complex and dynamic tissue that plays a central role in digestion, absorption, and waste elimination. Its function is regulated by intrinsic electrical activity, extrinsic neural and hormonal inputs, and interactions with specialized cells like ICC and PDGFRα+ cells.

Paralysis of Gastrointestinal Muscle

Paralysis of gastrointestinal smooth muscle can lead to conditions such as paralytic ileus and gastroparesis, which affect the normal movement of food through the digestive tract. Paralytic ileus occurs when the muscle contractions that move food through the intestines are temporarily paralyzed, leading to symptoms such as abdominal bloating, constipation, and nausea. Gastroparesis, on the other hand, involves the paralysis of the stomach muscles, causing delayed gastric emptying and symptoms like nausea, vomiting, and early satiety.

• Paralytic Ileus: This condition results from the temporary paralysis of the intestines, causing food and gas to accumulate, leading to symptoms such as abdominal distension, constipation, and nausea. It is often a side effect of surgery or other medical conditions.
• Gastroparesis: This condition involves the paralysis of the stomach muscles, leading to delayed gastric emptying. It can cause symptoms such as nausea, vomiting, and early satiety, and is often associated with diabetes or other underlying conditions.


Blood Sugar and Appetite with Gastroparesis

Gastroparesis, or paralysis of the gastrointestinal muscles, can significantly affect blood sugar levels and appetite. When the stomach muscles are paralyzed, food remains in the stomach for longer periods, leading to unpredictable absorption of nutrients and glucose into the bloodstream. This can cause erratic blood sugar levels, making it difficult to manage diabetes. Additionally, individuals may experience early satiety, nausea, vomiting, and a reduced appetite, which can lead to malnutrition and weight loss.
• Blood Sugar Fluctuations: The delayed emptying of the stomach can cause blood sugar levels to drop too low initially and then spike when food finally enters the small intestine, making it challenging to control diabetes.
• Appetite Changes: Paralyzed gastrointestinal muscles can lead to a feeling of fullness after eating small amounts of food, resulting in poor appetite and potential weight loss.


Muscle Mass & Metabolism
The loss of muscle mass significantly impacts the basal metabolic rate (BMR), as muscle tissue is metabolically active and requires more energy to maintain compared to fat tissue. As individuals age, they naturally lose muscle mass, which can lead to a decrease in BMR, making it easier to gain weight if calorie intake remains unchanged. This relationship between muscle mass and BMR is supported by various studies and health experts, emphasizing the importance of strength training and adequate protein intake to mitigate this decline.
• Muscle Mass and BMR: Muscle mass is a critical factor in determining BMR. The more muscle a person has, the higher their BMR, as muscle tissue burns more calories at rest compared to fat tissue.
• Age-Related Muscle Loss: After the age of 30, individuals typically lose 3–8% of their muscle mass each decade, which can significantly reduce BMR and contribute to weight gain if not counteracted by physical activity and proper nutrition.
• Impact of Strength Training: Engaging in regular strength training can help preserve and even increase muscle mass, thereby boosting BMR. This is recommended by health professionals as a key strategy for maintaining a healthy metabolism.
• Role of Protein Intake: Adequate protein consumption, especially after the age of 30, is essential for maintaining muscle mass and supporting a higher BMR. Protein helps in the repair and growth of muscle tissue, which is crucial for metabolic health.

GLP-1 and Muscle Loss
GLP-1 medications, such as Wegovy and Zepbound, can lead to significant weight loss, but they are associated with potential side effects, including poor appetite, loss of muscle mass, and a reduction in basal metabolic rate. The loss of muscle mass, known as sarcopenia, can result in decreased strength, stamina, and a lower resting metabolic rate. This muscle loss is often due to insufficient calorie and protein intake, which can occur as a result of the reduced appetite caused by GLP-1 medications. In a caloric deficit, the body may break down muscle tissue to meet energy needs, leading to a decrease in muscle protein synthesis and an increase in muscle protein breakdown.
The reduction in basal metabolic rate can make it more challenging to maintain weight loss, as the body’s energy expenditure decreases with the loss of muscle mass. This can lead to a plateau in weight loss and make it easier to regain weight after the initial loss. To mitigate these effects, it is important to maintain adequate protein intake and engage in regular physical activity to preserve muscle mass and support metabolic health.
Studies have shown that the loss of muscle mass with GLP-1 medications can vary, with some studies indicating that up to 39% of the total weight lost may be muscle mass. However, the impact of this loss on overall health and function can be mitigated through proper nutrition and exercise. Future research is needed to better understand the long-term effects of GLP-1 medications on muscle health and to develop strategies to preserve muscle mass during weight loss.

Eating Frequency and Blood Sugar
Eating every 3 to 4 hours can have a significant impact on blood sugar levels and metabolic rate, particularly for individuals with type 2 diabetes. This meal timing strategy helps maintain more stable blood sugar levels throughout the day by preventing large fluctuations that can occur with longer gaps between meals.
• Blood Sugar Regulation: Eating every 3 to 4 hours can help keep blood sugar levels lower during fasting periods and after meals, reducing the risk of spikes and crashes. This approach is particularly beneficial for individuals with type 2 diabetes, as it supports better glucose control.
• Metabolic Rate: While the direct effect of eating every 3 to 4 hours on metabolic rate is not explicitly detailed in the context, maintaining regular meal times can support a more consistent energy supply, which may help in sustaining metabolic processes.
Muscle Mass and Metabolism
Muscle mass plays a significant role in determining metabolic rate, as it is a metabolically active tissue that burns more calories than fat, even at rest. The more muscle mass a person has, the higher their resting metabolic rate (RMR) tends to be.
For example, one kilogram of muscle mass increases the basal metabolic rate by up to 100 calories per day.
Additionally, studies suggest that an increase in lean muscle mass can lead to a modest increase in RMR, with estimates ranging from 6 to 13 calories per day for every kilogram of muscle gained.
Moreover, resistance training can have a post-exercise calorie-burning effect known as excess post-exercise oxygen consumption (EPOC), where the body continues to burn calories after the workout.

Calories Burned at 140 BPM
To estimate the calories burned at a heart rate of 140 bpm for two individuals with different body compositions, we can use the formulas provided by calorie burn calculators that incorporate heart rate, weight, age, and duration of exercise. Since the exact age and duration of exercise are not specified, we will assume a standard duration of 60 minutes and an average age of 30 years for both individuals.
For the 150-pound man with 135 pounds of muscle, we will treat his effective metabolic weight as 150 pounds. For the 250-pound man with 195 pounds of muscle, we will use his total weight of 250 pounds. The formula used for men is:
Calories per minute=4.184−55.0969+(0.6309×Heart rate)+(0.1988×Weight)+(0.2017×Age)
Using this formula at a heart rate of 140 bpm:
• For the 150-pound man:
Calories per minute=4.184−55.0969+(0.6309×140)+(0.1988×150)+(0.2017×30)
This results in approximately 13.1 calories burned per minute, or 786 calories in 60 minutes.
• For the 250-pound man:
Calories per minute=4.184−55.0969+(0.6309×140)+(0.1988×250)+(0.2017×30)
This results in approximately 17.9 calories burned per minute, or 1,074 calories in 60 minutes.
Therefore, the difference in calories burned between the two individuals during 60 minutes of exercise at a heart rate of 140 bpm is approximately 288 calories, with the heavier individual burning more calories due to the greater body mass involved in the activity.