When it comes to learning, I like pictures. I like diagrams, charts, bullet points and graphs. Anything that helps me take what I've read and organize it into something neat and tidy. Mix in a touch of color and I'm the mayor of RETENTION CITY.
i'll go to the grave saying that education, the deeper understanding and visualization of our body systems, is one of most important part of putting together a cure for type 1 diabetes. Given that insulin release is priority number one for those with T1D, I think it's important to ensure that everyone has an opportunity to see the insulin cascade at work.
From this understanding we're then able to ask better questions. Getting straight answers from your mechanic is a lot easier when A) you know how your car's engine works and B) they're able to describe what they see knowing that you can understand them.
The same goes for the medical system. Ask better questions, get more targeted results.
Better questions only come when you know the material. So let's take a closer look at how your insulin is getting released. From this, we'll be armed to ask better questions about what we can do to re-ignite our beta cells.
STEP 1: INCOMING FOOD
Food Ingestion and Digestion:
Ingestion: Food is consumed and enters the digestive system, where it is broken down mechanically and chemically.
Digestion in the Stomach: Enzymes and stomach acid break down food into smaller particles.
Further Digestion in the Small Intestine: Partially digested food enters the small intestine, where it is further broken down by enzymes produced by the pancreas and the small intestine itself. Carbohydrates are broken down into simple sugars like glucose.
Absorption of Glucose:
Glucose Absorption: Glucose is absorbed through the walls of the small intestine and enters the bloodstream.
Transport to the Liver:
First Pass: Blood rich in nutrients, including glucose, travels through the portal vein to the liver. The liver acts as a buffer, regulating glucose release into the bloodstream.
Increase in Blood Glucose Levels:
Elevation of Blood Glucose: Following a meal, the glucose levels in the blood increase.
Detection by Pancreatic Beta Cells:
Pancreatic Beta Cells: Specialized cells in the islets of Langerhans within the pancreas detect the rise in blood glucose levels.
OK, press pause.
We eat the food. We chew it, swallow it and our stomach, pancreas and liver release digestive enzymes to break the food down for us to absorb.
Glucose is absorbed through the SMALL INTESTINE.
That freshly sugar-ified blood is passed through the LIVER first, where everything is pre-packaged and stored to allow for a proper beta cell response.
The ensuing increase in blood sugar (being governed by the liver) primes the beta cells to start releasing insulin.
STEP 2: THE BETA CELL RESPONSE
Glucose Uptake:
Glucose Transport: Glucose enters the beta cells through glucose transporter proteins, primarily GLUT2 in humans (or GLUT1 in rodents).
Glucose Metabolism:
Glycolysis and ATP Production: Inside the beta cell, glucose is metabolized through glycolysis, the citric acid cycle, and oxidative phosphorylation, resulting in the production of ATP.
ATP/ADP Ratio Change:
Increase in ATP: As glucose metabolism increases, the ATP/ADP ratio in the cell rises.
K_ATP Channel Closure:
KATP Channels: Beta cells have ATP-sensitive potassium (KATP) channels composed of SUR1 and Kir6.2 subunits. An increase in ATP binds to these channels, causing them to close.
Cell Membrane Depolarization: Closure of K_ATP channels leads to a reduction in potassium efflux, causing the cell membrane to depolarize.
Opening of Voltage-Gated Calcium Channels:
Calcium Influx: The depolarization of the membrane triggers the opening of voltage-gated calcium channels (L-type calcium channels), leading to an influx of calcium ions (Ca²⁺) into the cell.
Calcium-Induced Insulin Granule Exocytosis:
Calcium Signaling: The increase in intracellular calcium concentration is the key signal that triggers the exocytosis of insulin-containing granules.
Insulin Granules: Insulin is stored in secretory granules within the beta cells. The rise in intracellular Ca²⁺ promotes the movement of these granules to the plasma membrane.
Fusion and Release: Insulin granules fuse with the plasma membrane and release insulin into the bloodstream through a process mediated by the SNARE complex proteins.
Amplifying Pathways (Optional):
Secondary Signaling Molecules: In addition to the primary Ca²⁺ signal, other signaling molecules such as cyclic AMP (cAMP) and inositol 1,4,5-trisphosphate (IP3) can amplify the insulin release response.
cAMP Pathway: Agents like glucagon-like peptide-1 (GLP-1) can enhance cAMP production, which further amplifies insulin secretion through activation of protein kinase A (PKA) and Epac proteins.
Recapping the beta cell response:
Glucose passed through the liver enters the beta cells via the GLUT2 transporter membrane channel.
The beta cells use this glucose to create energy (ATP) for the cell's own functions.
As more glucose is coming in and once the beta cells have enough ATP, the increased amount of ATP signals the beta cell's potassium channels to CLOSE. This prevents potassium (K) from exiting the cell (called de-polarization).
The closure of the K channels initiates an influx of calcium into the cell. This calcium increase signals little pockets of stored insulin to bind to the cell membrane and dump insulin into the bloodstream.
Insulin sequesters the blood sugar into the cells. Once the blood sugar decreases, the potassium channels of the beta cells re-open, the cell is re-polarized and is now reset and ready to begin it's next cycle of insulin release.
Reading this opens up a lot of opportunities for questions relating to diabetes development. I'm going to highlight my personal points of interest that left me asking better questions and targeting better areas of interest.
Key Takeaways and Points of Interest:
The GUT
The gut and its ability to properly digest food, detect nutrients and absorb what's being eaten plays a major role in initiating an insulin response.
How many people that have T1D and T2D also have some sort of digestive issues? A lot.
Might how we're digesting our food affect the resulting cascade of absorption and allocation of nutrients?
How has food quality impacted our nutrient availability?
Might existing digestive issues be sabotaging our blood sugars? Or conversely, might our blood sugars be promoting poor gut health?
Leaky gut syndrome
IBS/Crohn's
Food sensitivities/allergies
How can we positively influence our gut microbiome to improve glycemic control?
The LIVER
As I've outlined in my iron-diabetes fascination, the liver has an undeniable role in pancreatic health. From detoxing and removing toxins to storing and distributing nutrients, if the liver is not healthy, the pancreas suffers for it.
What ailments, whether clinically recognized or not, might the liver experience that affect its ability to properly manage glucose levels in the first pass?
Fatty Liver Disease
Cirrhosis
Iron Overload
What other factors can impact my liver health?
Nutrition
Parasites
Viruses
Bacteria
Beta Cell Membranes
Beta cell membranes have to sense that the glucose is changing in order to engage insulin release mechanisms. Is there something wrong with the beta cell membranes that is not allowing proper GLUT2 function?
Beta Cell Mitochondria
Are the mitochondria of the beta cells effectively generating energy?
What are the consequences of faulty mitochondria on the health of the beta cell?
What are the necessary "ingredients" for optimal mitochondrial function?
What lifestyle factors are tied to disrupting/correcting those ingredients?
What are some common traits (and treatments) in other conditions with mitochondrial dysfunction?
Beta Cell Ion Channel Integrity
Potassium and calcium play important roles in initiating insulin release. What goes into coordinating proper ion channel function?
Are we potassium deficient?
Is there a specific balance of electrolytes that we need
What is an ideal sodium/potassium/calcium/magnesium balance?
Secondary Messengers
What additional ways can we positively influence the insulin cascade?
Are there supplemental strategies for improving the insulin cascade?
What are all the ways I can promote GLP-1 production?
Nutrition
Gut Health
Medication
What are natural sources of IP3?
I hope you come away with a little better understanding of the magic going on every time food passes our lips.
This is how my brain works. I learn the nuts and bolts of whats happening and then look for seams that pose a potential threat to our health. Once you identify the seam, list out the possible sources of dysfunction. Take those possible sources of overlay them with your personal health history. See what fits your story and then begin looking for ways to patch those holes.
Early on each seam opens up into a whole new, seemingly unrelated realm of health.
IE Magnesium deficiency impacts blood sugar, stress AND mental health?
You'll find that every facet of health is interconnected with 5+ more. Soon you'll recognize the amazing world going on inside our bodies and take commensurate care when introducing new health strategies.
It's rarely ever right or wrong, this or that. Mostly its a little bit of that, not too much of that. Remember to be consistent and understand that enacting change in a system deeply rooted in its faulty ways takes time. Build habits around those impactful changes, measure your progress over the long term and always be ready to make adjustments along the way.
Put those thinking caps on. Enjoy!
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