A potential important role of skeletal muscle in human counterregulation of hypoglycemia.
BACKGROUND
During hypoglycemia, systemic glucose uptake (SGU) decreases and endogenous glucose release (EGR) increases. Skeletal muscle appears to be primarily responsible for the reduced SGU and may be important for the increased EGR by providing lactate for gluconeogenesis (GN).


OBJECTIVE
The objective of the study was to test the hypothesis that reduced muscle glucose uptake and increased muscle lactate release both make major contributions to glucose counterregulation using systemic isotopic techniques in combination with forearm net balance measurements.


METHODS
The study was conducted at the University of Giessen Clinical Research Center.


METHODS
Nine healthy volunteers participated in the study.


METHODS
A 2-h hyperinsulinemic euglycemic clamp (blood glucose approximately 4.4 mm) was followed by a 90-min hypoglycemic clamp (blood glucose approximately 2.6 mm).


RESULTS
Compared with the euglycemic clamp, SGU decreased (21.0 +/- 2.0 vs. 29.6 +/- 1.8 micromol.kg body weight(-1).min(-1); P < 0.001), whereas EGR (11.2 +/- 1.7 vs. 4.9 +/- 1.3 micromol.kg body weight(-1) .min(-1); P < 0.003), arterial lactate concentrations (1051 +/- 162 vs. 907 +/- 115 microm; P < 0.02), systemic lactate release (23.5 +/- 0.9 vs. 17.1 +/- 0.9 micromol.kg body weight(-1).min(-1); P < 0.001), and lactate GN (4.50 +/- 0.60 vs. 2.74 +/- 0.30 micromol.kg body weight(-1).min(-1); P < 0.02) increased during hypoglycemia; the proportion of lactate used for GN remained unchanged (38 +/- 4 vs. 32 +/- 3%; P = 0.27). Whole-body muscle glucose uptake decreased approximately 50% during hypoglycemia (6.4 +/- 1.9 vs. 13.6 +/- 2.9 micromol.kg body weight(-1).min(-1); P < 0.001), which accounted for approximately 85% of the reduction of SGU. Whole-body muscle lactate release increased 6.6 +/- 1.6 micromol.kg body weight(-1). min(-1) (P < 0.01), which could have accounted for all the increase in systemic lactate release and, considering the proportion of lactate used for GN, contributed 1.4 +/- 0.4 micromol.kg body weight(-1).min(-1) (approximately 25%) to the increase in EGR.


CONCLUSIONS
Reduced muscle glucose uptake and increased muscle lactate release both make major contributions to glucose counterregulation in humans.
Meyer
Christian
C
Carl T. Hayden Veteran Affairs Medical Center, Department of Endocrinology, 650 East Indian School Road, Phoenix, Arizona 85012, USA. christian.meyer@med.va.gov
Saar
Petra
P
Soydan
Nedim
N
Eckhard
Michael
M
Bretzel
Reinhard G
RG
Gerich
John
J
Linn
Thomas
T
D000328:Adult; D000409:Alanine / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005542:Forearm / Q000098:blood supply; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D050261:Glycogenolysis; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*
D001786:Blood Glucose; D019344:Lactic Acid; D005947:Glucose; D000409:Alanine