Effect of hemipancreatectomy and of pancreatic diversion on the tolerance to a glucose load in humans.
BACKGROUND
The role of the pattern, quantity and site of insulin secretion in the tolerance to a glucose challenge is not fully evaluated in humans because it is difficult to obtain appropriate clinical models.


METHODS
To address this issue, we studied subjects with reduced pancreatic mass (hemipancreatectomized, HEMI), systemic insulin delivery (pancreas transplant recipients, PTX), and two control groups (healthy, CON; and with uveitis on the same immunosuppression as PTX, UVE), with an hyperglycaemic clamp (study 1, + 4.2 mmol L-1), using a repeat experiment (study 2) with a fixed glucose infusion, calculated to increase by 35% that in study 1.


RESULTS
In study 1, CON increased glucose uptake to 20 +/- 3 micromol kg-1 min-1 after a biphasic insulin response. In study 2, CON further increased the glucose uptake via an increment in prehepatic insulin secretion that stimulated insulin sensitivity without changes in peripheral insulin and glucose concentrations. HEMI and PTX had 35% less glucose uptake in study 1, compared to CON, and increased glucose concentrations (+ 1.6 mmol L-1) in study 2. UVE had an intermediate defect. The causes of intolerance were different: HEMI had a defective first-phase insulin secretion (50% peripheral insulin concentrations) but maintained insulin sensitivity; PTX had normal peripheral insulin but only one-third of the insulin sensitivity of CON.


CONCLUSIONS
Hemipancreatectomy and systemic insulin delivery impair first-phase insulin secretion; second-phase peripheral insulinization (HEMI); insulin sensitivity (PTX); and a mechanism evidentiated in study 2 of CON that increases insulin sensitivity in response to prehepatic insulin secretion (both groups). Failure of these mechanisms is largely compensated by hyperglycaemia.
Battezzati
A
A
Istituto Scientifico San Raffaele, Milano, Italy.
Zerbi
A
A
Perseghin
G
G
Caumo
A
A
Terruzzi
I
I
Di Carlo
V
V
Luzi
L
L
D000328:Adult; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005246:Feedback / Q000502:physiology; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000493:pharmacokinetics; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006943:Hyperglycemia / Q000175:diagnosis / Q000378:metabolism; D007165:Immunosuppression Therapy; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D010180:Pancreatectomy
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005934:Glucagon; D005947:Glucose; D006854:Hydrocortisone