TY - JOUR
T1 - Glycogen metabolism is impaired in the brain of male type 2 diabetic Goto-Kakizaki rats
AU - Soares, Ana Francisca
AU - Nissen, Jakob D.
AU - Garcia-Serrano, Alba M.
AU - Nussbaum, Sakura S.
AU - Waagepetersen, Helle S.
AU - Duarte, João M.N.
PY - 2019/8
Y1 - 2019/8
N2 -
Diabetes impacts the central nervous system predisposing to cognitive decline. While glucose is the main source of energy fueling the adult brain, brain glycogen is necessary for adequate neuronal function, synaptic plasticity and memory. In this study, we tested the hypothesis that brain glycogen metabolism is impaired in type 2 diabetes (T2D).
13
C magnetic resonance spectroscopy (MRS) during [1-
13
C]glucose i.v. infusion was employed to detect
13
C incorporation into whole-brain glycogen in male Goto-Kakizaki (GK) rats, a lean model of T2D, and control Wistar rats. Labeling from [1-
13
C]glucose into brain glycogen occurred at a rate of 0.25 ± 0.12 and 0.48 ± 0.22 µmol/g/h in GK and Wistar rats, respectively (p = 0.028), despite similar brain glycogen concentrations. In addition, the appearance of [1-
13
C]glucose in the brain was used to evaluate glucose transport and consumption. T2D caused a 31% reduction (p = 0.031) of the apparent maximum transport rate (T
max
) and a tendency for reduced cerebral metabolic rate of glucose (CMR
glc
; −29%, p = 0.062), indicating impaired glucose utilization in T2D. After MRS in vivo, gas chromatography-mass spectrometry was employed to measure regional
13
C fractional enrichment of glucose and glycogen in the cortex, hippocampus, striatum, and hypothalamus. The diabetes-induced reduction in glycogen labeling was most prominent in the hippocampus and hypothalamus, which are crucial for memory and energy homeostasis, respectively. These findings were further supported by changes in the phosphorylation rate of glycogen synthase, as analyzed by Western blotting. Altogether, the present results indicate that T2D is associated with impaired brain glycogen metabolism.
AB -
Diabetes impacts the central nervous system predisposing to cognitive decline. While glucose is the main source of energy fueling the adult brain, brain glycogen is necessary for adequate neuronal function, synaptic plasticity and memory. In this study, we tested the hypothesis that brain glycogen metabolism is impaired in type 2 diabetes (T2D).
13
C magnetic resonance spectroscopy (MRS) during [1-
13
C]glucose i.v. infusion was employed to detect
13
C incorporation into whole-brain glycogen in male Goto-Kakizaki (GK) rats, a lean model of T2D, and control Wistar rats. Labeling from [1-
13
C]glucose into brain glycogen occurred at a rate of 0.25 ± 0.12 and 0.48 ± 0.22 µmol/g/h in GK and Wistar rats, respectively (p = 0.028), despite similar brain glycogen concentrations. In addition, the appearance of [1-
13
C]glucose in the brain was used to evaluate glucose transport and consumption. T2D caused a 31% reduction (p = 0.031) of the apparent maximum transport rate (T
max
) and a tendency for reduced cerebral metabolic rate of glucose (CMR
glc
; −29%, p = 0.062), indicating impaired glucose utilization in T2D. After MRS in vivo, gas chromatography-mass spectrometry was employed to measure regional
13
C fractional enrichment of glucose and glycogen in the cortex, hippocampus, striatum, and hypothalamus. The diabetes-induced reduction in glycogen labeling was most prominent in the hippocampus and hypothalamus, which are crucial for memory and energy homeostasis, respectively. These findings were further supported by changes in the phosphorylation rate of glycogen synthase, as analyzed by Western blotting. Altogether, the present results indicate that T2D is associated with impaired brain glycogen metabolism.
KW - brain metabolism
KW - diabetes
KW - glucose
KW - glycogen
KW - insulin resistance
UR - http://www.scopus.com/inward/record.url?scp=85065245191&partnerID=8YFLogxK
U2 - 10.1002/jnr.24437
DO - 10.1002/jnr.24437
M3 - Journal article
C2 - 31044444
AN - SCOPUS:85065245191
SN - 0360-4012
VL - 97
SP - 1004
EP - 1017
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
ER -
