DIABETES/METABOLIC SYNDROME

There is so much information to share on this page! Today, as I start the page it is to introduce a particular topic, but I will be back to populate the page with very much more!

GLP-1: What is it? What's all the fuss?

Today, all the rage when it comes to diabetes and obesity problems are the GLP-1 receptor agonists, such as Ozempic and Wegovy. These drugs are currently being promoted and advertised heavily. What isn't being shouted so loudly from the rooftops is their many concerning side effects and potential longterm negative health impacts. Let's dig a bit deeper into understanding GLP-1, it's influence on health, and how we can naturally increase its activity without sucommbing to potentially dangerous medications. Click above to view my Webinar presentation of the info below.

GLP-1 (Glucagon-Like Peptide-1) is an incretin hormone primarily produced by the intestinal L-cells in response to food intake. It plays several key roles in metabolic regulation:

Insulin Secretion: Enhances insulin release from the pancreas when blood glucose levels rise.
Glucagon Suppression: Helps reduce the secretion of glucagon, a hormone that increases blood sugar levels.
Gastric Emptying: Slows the rate at which the stomach empties, contributing to a more gradual rise in blood glucose.
Appetite Regulation: Promotes feelings of fullness, which can help control appetite and food intake.

These functions make GLP-1 an important target for treatments aimed at managing type 2 diabetes and obesity.

How do the GLP-1 receptor agonist medications work?

GLP-1 receptor agonist drugs are designed to mimic the actions of the naturally occurring incretin hormone GLP-1. Here’s a breakdown of how they work:

Mimicking Natural GLP-1:
These drugs bind to GLP-1 receptors, just as endogenous GLP-1 would, thereby activating them.
Enhancing Insulin Secretion:
They stimulate pancreatic beta cells to secrete insulin in a glucose-dependent manner. This means that insulin is released more effectively when blood glucose levels are high.
Suppressing Glucagon Release:
By inhibiting the release of glucagon from pancreatic alpha cells, these drugs help reduce the production of glucose by the liver.
Slowing Gastric Emptying:
They delay the emptying of the stomach, which leads to a slower and more controlled absorption of glucose after meals, reducing postprandial blood sugar spikes.
Reducing Appetite:
These agents also act on the brain to promote satiety, which can contribute to reduced food intake and potential weight loss.
Prolonged Activity:
GLP-1 receptor agonists are engineered to be resistant to degradation by the enzyme DPP-IV (dipeptidyl peptidase-IV), giving them a longer duration of action compared to natural GLP-1.

Overall, by enhancing insulin secretion, suppressing glucagon, slowing gastric emptying, and reducing appetite, GLP-1 receptor agonists help improve glycemic control and support weight management, making them valuable in the treatment of type 2 diabetes and obesity.

"What about side effects? "

Gastrointestinal Disturbances:
Nausea, vomiting, diarrhea, and sometimes constipation are very common, especially when starting therapy. These symptoms often lessen over time as the body adjusts.
Pancreatitis Risk:
There have been reports of acute pancreatitis in patients using these drugs, so patients are advised to watch for symptoms like severe abdominal pain.
Thyroid C-Cell Tumors:
Some GLP-1 receptor agonists carry a boxed warning regarding an increased risk of thyroid C-cell tumors, based on animal studies. This risk leads to caution in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.
Other Considerations:
There may also be concerns regarding effects on kidney function and, in some cases, gallbladder disease.
- Diabetic Retinopathy Concerns:
  In clinical trials—especially with semaglutide—there have been reports of an increased incidence of diabetic retinopathy complications. These complications can include worsening of pre-existing retinal issues, potentially leading to visual disturbances. The prevailing view is that rapid improvement in blood glucose control, rather than a direct toxic effect on the eyes, may trigger these changes.
- Gastroparesis - impaired intestinal motility - i.e., "constipation that won't go away..."
  - Transient Effect:
    The delay in gastric emptying is typically transient. Many patients experience these effects primarily when initiating treatment, and the body often adjusts over time.
  - Exacerbation in Susceptible Individuals:
    In patients who already have gastroparesis or underlying gastrointestinal motility issues—commonly seen in some individuals with diabetes—GLP-1 receptor agonists might worsen or unmask symptoms. This doesn't necessarily mean the drug causes new, long-term gastroparesis, but it can aggravate pre-existing conditions.

POTENTIAL SIDE EFFECTS

What can I do to impact GLP-1 without using these drugs?

Introducing Akkermansia

What is Akkermansia? Let's Explore!

Akkermansia and GLP-1

Akkermansia muciniphila isn’t a direct GLP-1 receptor agonist, but its presence in the gut indirectly supports increased GLP-1 secretion, leading to beneficial metabolic effects:

Mucin Degradation:
Akkermansia degrades the mucus layer in the gut, a process that promotes gut barrier integrity and renewal.
Cross-Feeding Mechanism:
The byproducts from mucin breakdown serve as nutrients for other gut bacteria. These bacteria, in turn, produce short-chain fatty acids (SCFAs) like butyrate, which stimulate the gut’s L-cells.
Enhanced GLP-1 Secretion:
SCFAs encourage L-cells to secrete GLP-1, an incretin hormone that helps regulate insulin, appetite, and overall energy balance.
Therapeutic Implications:
Improved endogenous GLP-1 levels contribute to metabolic health, making Akkermansia a promising candidate for next-generation probiotic strategies aimed at managing conditions like type 2 diabetes and obesity.

This interplay between Akkermansia’s activity and GLP-1 secretion highlights how modulating the gut microbiome can indirectly foster beneficial hormonal responses in the body.

Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice

Abstract

The gut microbiota, which includes Akkermansia muciniphila, is known to modulate energy metabolism, glucose tolerance, immune system maturation and function in humans1-4. Although A. muciniphila is correlated with metabolic diseases and its beneficial causal effects were reported on host metabolism5-8, the molecular mechanisms involved have not been identified. Here, we report that A. muciniphila increases thermogenesis and glucagon-like peptide-1 (GLP-1) secretion in high-fat-diet (HFD)-induced C57BL/6J mice by induction of uncoupling protein 1 in brown adipose tissue and systemic GLP-1 secretion. We apply fast protein liquid chromatography and liquid chromatography coupled to mass spectrophotometry analysis to identify an 84 kDa protein, named P9, that is secreted by A. muciniphila. Using L cells and mice fed on an HFD, we show that purified P9 alone is sufficient to induce GLP-1 secretion and brown adipose tissue thermogenesis. Using ligand-receptor capture analysis, we find that P9 interacts with intercellular adhesion molecule 2 (ICAM-2). Interleukin-6 deficiency abrogates the effects of P9 in glucose homeostasis and downregulates ICAM-2 expression. Our results show that the interactions between P9 and ICAM-2 could be targeted by therapeutics for metabolic diseases.

Fact-Checking The 4 Most Popular Akkermansia Claims

Butryate & GLP-1

I have an entire page dedicated to butyrate, so I won't belabor the introduction here. Please go HERE to learn much more about what butyrate is and its health benefits.

Butyrate, a short-chain fatty acid produced by the fermentation of dietary fibers by gut bacteria, plays an important role in stimulating the release of GLP-1 from intestinal L-cells. Here’s how their interaction works:

Stimulation of GLP-1 Secretion:
Butyrate activates G-protein coupled receptors such as GPR41 and GPR43 on L-cells. This receptor engagement triggers intracellular signaling pathways that promote the secretion of GLP-1, an incretin hormone that helps regulate insulin release and blood glucose levels.
Metabolic Benefits:
By enhancing GLP-1 release, butyrate indirectly supports improved glycemic control, increased insulin sensitivity, and appetite regulation. These effects contribute to better overall metabolic health and may help mitigate conditions like type 2 diabetes.
Dual Role in Gut Health:
In addition to promoting GLP-1 secretion, butyrate serves as a key energy source for colonocytes (cells lining the colon) and exhibits anti-inflammatory properties. Its actions help maintain a healthy gut environment, further supporting the proper functioning of the enteroendocrine system.

Overall, the interaction between butyrate and GLP-1 illustrates a vital link between dietary fiber, the gut microbiota, and metabolic regulation—highlighting how naturally produced metabolites can have far-reaching effects on human health.

Anything Else?

Beyond Akkermansia & butyrate, several natural approaches and compounds are being explored for their ability to enhance GLP-1 secretion and improve metabolic health:

Dietary Fiber and Prebiotics:
Consuming high-fiber foods, prebiotics, and resistant starch can promote the production of short-chain fatty acids (SCFAs) like butyrate and propionate through fermentation by gut microbes. These SCFAs are known to stimulate the L-cells in the gut to secrete GLP-1.
Other Probiotics and Fermented Foods:
Beyond Akkermansia, strains of Lactobacillus and Bifidobacterium—commonly found in fermented foods such as yogurt, kefir, and sauerkraut—can help maintain a healthy gut environment that favors GLP-1 release.
Plant-Derived Compounds:
Several bioactive compounds found in plants have been investigated for their potential to modulate GLP-1:
- Berberine: An alkaloid found in plants like goldenseal and barberry, which has been shown to influence the gut microbiota and may enhance GLP-1 secretion.
- Curcumin: The active ingredient in turmeric, associated with improved insulin sensitivity and anti-inflammatory effects, might also play a role in GLP-1 modulation.
- Polyphenols: Compounds in foods such as green tea, cocoa, and berries have been suggested to affect gut hormone levels, including GLP-1, although more research is needed to clarify these effects.

These natural strategies work primarily by improving gut health and creating an environment that supports the release of GLP-1 from intestinal L-cells. While the evidence is promising, further research is ongoing to fully understand and optimize these natural interventions for metabolic health.