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Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT
Published on: January 7, 2018
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A decrease in plasma glucose levels is required for increased endogenous glucose production with a single
Nozomu Yamasaki1, Yoshifumi Tamura1,2, Hideyoshi Kaga1
1Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Diabetes, Obesity & Metabolism
|December 30, 2020
Summary
The sodium-glucose co-transporter-2 (SGLT2) inhibitor tofogliflozin decreases plasma glucose (PG). This PG reduction is necessary for increased endogenous glucose production (EGP) and reduced insulin secretion, as seen in type 2 diabetes patients.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Pharmacology
Background:
- Type 2 diabetes is characterized by impaired glucose regulation.
- Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a class of antidiabetic drugs.
- Understanding the precise mechanisms of SGLT2 inhibitors is crucial for optimizing diabetes management.
Purpose of the Study:
- To investigate the impact of tofogliflozin on endogenous glucose production (EGP).
- To determine if reduced plasma glucose (PG) levels trigger changes in EGP, insulin, and glucagon.
- To elucidate the role of PG decrease in mediating the effects of SGLT2 inhibitors.
Main Methods:
- A study involving 12 Japanese patients with type 2 diabetes.
- Evaluation of EGP under three conditions: no drug (CON), tofogliflozin (TOF), and TOF with glucose infusion to normalize PG (TOF+G).
- Measurement of EGP, C-peptide (an insulin marker), and glucagon levels over 180 minutes.
Main Results:
- Endogenous glucose production decreased significantly in CON and TOF+G, but not in TOF alone.
- A greater decrease in C-peptide (insulin secretion) was observed with TOF compared to CON and TOF+G.
- Glucagon levels increased significantly with TOF, but not significantly with TOF+G compared to CON.
Conclusions:
- The observed increase in EGP and decrease in insulin secretion are dependent on the reduction in plasma glucose levels induced by SGLT2 inhibitors.
- This finding highlights the glucose-lowering effect as the primary driver for hormonal and metabolic adjustments.
- These insights contribute to understanding the glycemic control mechanisms of SGLT2 inhibitors in type 2 diabetes.
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