Dr. Banting’s Hypothesis: Part I

In today’s blog, we will begin to unravel the meaning behind Dr. Banting’s hypothesis by discussing the anatomy of the digestive system, microscopic structure of the pancreas and blood glucose regulation by the hormone insulin. During his 10-month stay here in London, Dr. Banting held a teaching position at the University of Western Ontario in the Department of Surgery and Physiology. In late October 1920, he was asked to prepare a lecture on the anatomical features of the pancreas and its role in carbohydrate metabolism. On the evening of October 30, 1920 Dr. Banting read an article written by Dr. Moses Baron, that discussed an autopsy report of a patient with diabetes whose pancreatic duct had been obstructed by stones (a condition called pancreatic lithiasis) and he had a eureka moment! He rose from his bed at 2 am on October 31, 1920 to jot down his 25-word hypothesis pertaining to the extraction of a hypothetical pancreatic hormone (later referred to as insulin).

His hypothesis read as follows:

Diabetus [sic]. Ligate pancreatic ducts of dog. Keep dogs alive till acini degenerate leaving islets. Try to isolate the internal secretion of these and relieve glycosurea [sic].

Sounds like a lot of scientific jargon, but what exactly does Dr. Banting’s hypothesis mean?

Pancreatic duct, acini and islets mentioned in the hypothesis are anatomical terms, so let’s start with the anatomy of the digestive system.

Digestive System Gross Anatomy

The digestive system consists of

• the gastrointenstinal (GI) tract and
• accessory organs (e.g. pancreas, liver, gallbladder and salivary glands).

The GI tract begins at the mouth and ends at the anus.

After you’ve chewed and swallowed your food, it travels down your esophagus before reaching your stomach. Food (now referred to as bolus) is partially digested by stomach/gastric acid before being pushed through a valve into the first part of the small intestine, the duodenum.

What happens in the duodenum?

Duodenum, Pancreas and Pancreatic Duct

In the duodenum (depicted as a pink structure on the left side of the diagram below), food (now referred to as chyme) is further digested by specialized proteins called enzymes. So where do these digestive enzymes come from?

• They are produced by the pancreas, a tadpole-shaped organ positioned behind the stomach and below your ribcage (depicted as a beige structure in the diagram below).
• They are transported to the small intestine via a tube inside the pancreas called the pancreatic duct.

Now, let’s take a closer look at the overall structure of the pancreas.

If you were to take a tissue sample of the pancreas, stain it and place it under the microscope you would notice

• lighter staining tissue (depicted as dark pink cell clusters in the inset diagram above)
  • produces hormones
  • hormones are chemical messengers that allow for communication between organs and travel long distances through the bloodstream
  • constitutes the endocrine¹ portion of the pancreas.
• darker staining tissue (depicted as blue cell clusters in the inset diagram above)
  • produces digestive enzymes
  • constitutes the exocrine² portion of the pancreas.

How are these structures organized inside the pancreas?

Acini and Islets of Langerhans

In a cross-section of the pancreas, we find cell clusters (lobules) called acini ³ (blue structures in the inset diagram above).

• Acini release/secrete their products (enzymes) into small canals (intralobular and interlobular ducts).
• These small canals in turn merge to form the larger pancreatic duct which empties its contents into the duodenum.

Acini surround lobules called islets of Langerhans (pink structures in the inset diagram above).

• These pancreatic islets resemble small islands and secrete their products (hormones) into the bloodstream.

Islets of Langerhans: Alpha and Beta Cells

Islets of Langerhans consist of different cell types that are involved in regulating glucose levels.

• Beta cells
  • produce insulin, a hormone that lowers blood glucose
  • insulin is useful for hyperglycemic patients (i.e. patients with high blood glucose).
• Alpha cells
  • produce glucagon, a hormone that increases blood glucose
  • glucagon therefore has the opposite effect of insulin.

How does insulin lower blood glucose?

Blood Glucose Regulation

Let’s suppose that your pancreas has released enzymes into the duodenum in order to digest a pretzel you’ve eaten into simple sugars/carbohydrates (e.g. glucose). At this point, glucose is absorbed across the walls of your small intestine into the bloodstream. This leads to an increase in blood glucose. The beta cells of your pancreas sense this increase and start producing insulin. Insulin then travels through your bloodstream and ends up targeting many tissues including liver, muscle and fat (or adipose tissue).

• Excess glucose is uptaken by liver and muscle.
  • It is stored in the form of glycogen (a chain/polymer of glucose molecules) in these organs.
• Excess glucose is also uptaken by adipose tissue cells (adipocytes)
  • Adipocytes store glucose as fat (triglycerides).

The end result is that glucose is removed from the bloodstream and blood glucose levels fall within a healthy range.

In summary,

The pancreas

• is a tadpole-shaped organ
• is part of the digestive system as well as the endocrine system
• consists of acini (exocrine tissue) and islets of Langerhans (endocrine tissue).

Acini

• produce digestive proteins (enzymes)
• release enzymes into the pancreatic duct which empties into the duodenum (first part of the small intestine).

Beta cells

• are found within the islets of Langerhans
• produce the hormone insulin
  • insulin is released into the bloodstream and targets many tissues.

Insulin lowers blood glucose

• How?
  • Promotes glucose uptake.
• Where?
  • In many tissues including liver, muscle and fat (adipose tissue).

Glucose is stored as

• glycogen (long chain of glucose molecules) in muscle and liver
• fat (triglycerides) in adipose tissue.

We will later take a closer look at insulin signaling, discuss what happens in patients with diabetes mellitus and conclude with a detailed explanation of Dr. Banting’s hypothesis.

Notes 

1.Endocrine: relates to glands that release/secrete hormones directly into the bloodstream. These secretions are considered internal. Back

2. Exocrine: relates to glands that release/secrete their products into ducts instead of directly into the bloodstream. These secretions are considered external. Back

3. Acini is the plural form of acinus. Back

References

1. Marion, E.N., Mallatt J., & Wilhelm, P.B. (2008). Human Anatomy (5th ed.). San Francisco, CA: Pearson Benjamin Cummings.

2. Kumar V. et al. (2007). Robbins Basic Pathology (8th ed.). Philadelphia, PA: Saunders Elsevier.

3. BruceBlaus. (2013, Sept 5). Blausen Medical Communications. Retrieved from the Wikimedia commons Web site: http://upload.wikimedia.org/wikipedia/commons/1/14/Blausen_0316_DigestiveSystem.png

4. OpenStax College. (2013, June 19). Anatomy & Physiology. Retrieved from the Connexions Web site: http://cnx.org/content/col11496/1.6/