The Role of Pulsatile Insulin Secretion (A Study Investigating the Effects of Partial Pacreatectomy on Glucose Metabolism)

Beta cells of the pancreas are the insulin producing cells. People with impaired fasting
glucose have a beta cell mass ~50% of that of normal glucose tolerant subjects.

A 2006 canine study by Dr. Peter Butler's group at UCLA demonstrated that glucose stimulated
insulin secretion was deficient after 50% decrease in beta cell mass after distal
pancreatectomy compared to those dogs who had sham surgery. The pancreatectomized dogs had
impaired fasting glucose with impaired insulin secretion and insulin resistance. The
decreased insulin secretion was a result of decreased insulin secretory pulses or bursts
with no change seen in pulse frequency, the same pattern seen in humans with Type 2
diabetes. Conclusions derived from this study include the following:

1. When beta cell mass declines to ~50% the capacity for the remaining beta cells to
secrete insulin in appropriate secretory bursts is compromised, leading to a deficit in
insulin secretion most obvious on glucose stimulation.

2. The decreased insulin burst mass results in an additional component of insulin
resistance, and this together with the compromised capacity for insulin secretion leads
to decompensation of glucose regulation and diabetes onset.

How does this translate in humans who have had partial pancreatectomy? In 1990, Kendall and
colleagues published a study looking at the effects of hemipancreatectomy in healthy human
subjects on insulin secretion and glucose tolerance. These subjects were donors for
pancreatic transplantation. They showed that fasting insulin and c-peptide levels were lower
one year after hemipancreatectomy. Seven of the 28 donors had abnormal glucose tolerance one
year after hemipancreatectomy, but all 28 had normal fasting plasma glucose levels. This
study and others like it confirm the development of impaired glucose tolerance after partial
pancreatectomy, but pulsatile insulin secretion and hepatic insulin clearance were not
measured.

As stated above, the main objective of this pilot study is to establish and quantify the
impact of a deficit in beta cell mass, due to partial pancreatectomy for benign tumors, on
glucose tolerance. Results of this study may be used to develop a future metabolic study
that uses glucose isotopes to establish the effects of partial pancreatectomy on glucose
tolerance, basal and stimulated insulin secretion as well as hepatic and extrahepatic
insulin sensitivity under conditions of usual physiology. This will enable us to further
understand the relationship between loss of beta cells, decreased insulin secretion and
increased insulin resistance in humans.

Inclusion Criteria:

- Male and Female subjects

- 18-80 years of age who have had

- partial pancreatectomy due to a benign lesion

- OR are healthy control subjects

- are willing to fast (nothing to eat or drink for 10 hours)prior to visits

Exclusion Criteria:

- Pancreatic malignancy

- Chronic pancreatitis

- Pregnant

- On steroid medications such as prednisone