Comparison of Glucagon Stimulation Test and Insulin Tolerance Test for Assessment of an Anterior Pituitary Function-A

Krzysztof C Lewandowski1, Joanna Kawalec2, Paulina Lewandowska3

  • 1Faculty of Medicine-Collegium Medicum, Mazovian University in Plock, Dąbrowskiego St. 2, 09-402 Plock, Poland.

Journal of Clinical Medicine
|September 27, 2025
PubMed

Background: The insulin tolerance test (ITT) and glucagon stimulation test (GST) are commonly used for assessment of anterior pituitary function, but there are few direct comparisons of these tests, i.e., where both tests were performed on the same individuals. Methods: We designed a cross-over study, where we compared concentrations of glucose, cortisol, and GH during ITT and standard fixed-dose GST in 19 subjects (five males), with a mean age of 33.8 years (range 19-60) and a mean BMI of 27.8 kg/m2 (range 16.5-47.6). Results: Optimal fall in glucose concentrations during ITT (i.e., <40 mg/dL) was obtained in all study participants. During ITT we obtained lower minimal glucose concentrations (glucose nadir), i.e., 29.7 ± 7.67 mg/dL at 30 min of ITT, than during GST, i.e., 73.6 ± 9.67 mg/dL at 180 min of GST, p < 0.01. In contrast, glucose fluctuations (ΔGlucose) were higher during GST (77.8 ± 22.6 mg/dL versus 56.7 ± 10.9 mg/dL, p = 0.002, for GST and ITT, respectively). There was, however, no difference in degree of stimulation of either cortisol or GH release during both tests: ΔCortisol 9.28 ± 3.79 µg/dL for GST versus 8.49 ± 3.46 µg/dL for ITT, p = 0.4, and ΔGH 10.23 ± 10.36 ng/mL for GST versus 10.52 ± 9.67 ng/mL for ITT, p = 1.0. Conclusions: Although hypoglycaemia is not observed during GST in contrast to ITT, it appears that both tests lead to similar increments in cortisol and growth hormone secretion. We, therefore, conclude that GST should not be automatically considered as an "inferior" option in comparison to ITT.

Related Concept Videos

Hypoglycemia and Glucagon01:15

Hypoglycemia and Glucagon

Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
835
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
6.4K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
2.2K
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
848
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
600