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Article

Mechanism of Action of Inhaled Insulin on Whole Body Glucose Metabolism in Subjects with Type 2 Diabetes Mellitus

1
Diabetes Division, Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA
2
Cardiometabolic Risk Laboratory, Institute of Clinical Physiology, 56124 Pisa, Italy
3
South Texas Veteran Health Care System, San Antonio, TX 78229, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(17), 4230; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20174230
Received: 7 May 2019 / Revised: 21 August 2019 / Accepted: 22 August 2019 / Published: 29 August 2019
In the current study we investigate the mechanisms of action of short acting inhaled insulin Exubera®, on hepatic glucose production (HGP), plasma glucose and free fatty acid (FFA) concentrations. 11 T2D (Type 2 Diabetes) subjects (age = 53 ± 3 years) were studied at baseline (BAS) and after 16-weeks of Exubera® treatment. At BAS and after 16-weeks subjects received: measurement of HGP (3-3H-glucose); oral glucose tolerance test (OGTT); and a 24-h plasma glucose (24-h PG) profile. At end of study (EOS) we observed a significant decrease in fasting plasma glucose (FPG, 215 ± 15 to 137 ± 11 mg/dl), 2-hour plasma glucose (2-h PG, 309 ± 9 to 264 ± 11 mg/dl), glycated hemoglobin (HbA1c, 10.3 ± 0.5% to 7.5 ± 0.3%,), mean 24-h PG profile (212 ± 17 to 141 ± 8 mg/dl), FFA fasting (665 ± 106 to 479 ± 61 μM), post-OGTT (433 ± 83 to 239 ± 28 μM), and triglyceride (213 ± 39 to 120 ± 14 mg/dl), while high density cholesterol (HDL-C) increased (35 ± 3 to 47 ± 9 mg/dl). The basal HGP decreased significantly and the insulin secretion/insulin resistance (disposition) index increased significantly. There were no episodes of hypoglycemia and no change in pulmonary function at EOS. After 16-weeks of inhaled insulin Exubera® we observed a marked improvement in glycemic control by decreasing HGP and 24-h PG profile, and decreased FFA and triglyceride concentrations. View Full-Text
Keywords: inhaled insulin; whole body glucose metabolism; hepatic glucose production; tracers; OGTT; disposition index inhaled insulin; whole body glucose metabolism; hepatic glucose production; tracers; OGTT; disposition index
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MDPI and ACS Style

Mehta, R.J.; Gastaldelli, A.; Balas, B.; Ricotti, A.; DeFronzo, R.A.; Tripathy, D. Mechanism of Action of Inhaled Insulin on Whole Body Glucose Metabolism in Subjects with Type 2 Diabetes Mellitus. Int. J. Mol. Sci. 2019, 20, 4230. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20174230

AMA Style

Mehta RJ, Gastaldelli A, Balas B, Ricotti A, DeFronzo RA, Tripathy D. Mechanism of Action of Inhaled Insulin on Whole Body Glucose Metabolism in Subjects with Type 2 Diabetes Mellitus. International Journal of Molecular Sciences. 2019; 20(17):4230. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20174230

Chicago/Turabian Style

Mehta, Rucha J., Amalia Gastaldelli, Bogdana Balas, Andrea Ricotti, Ralph A. DeFronzo, and Devjit Tripathy. 2019. "Mechanism of Action of Inhaled Insulin on Whole Body Glucose Metabolism in Subjects with Type 2 Diabetes Mellitus" International Journal of Molecular Sciences 20, no. 17: 4230. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20174230

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