The Impact of Diabetes on the CNS

McCall, Anthony L.

doi:10.2337/diab.41.5.557

Cited by 254 publications

(82 citation statements)

References 191 publications

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“…There is evidence of abnormal NE neurotransmission in diabetic animals. Hypothalamic NE turnover, an index of NE utilization, was found to be decreased in male and female rats with STZ-induced diabetes [18, 19, 20]. Other neurotransmitter levels have also been shown to be altered by diabetes [21, 22, 23].…”

Section: Discussionmentioning

confidence: 99%

Central Insulin Administration Maintains Reproductive Behavior in Diabetic Female Rats

Kovács

Morales²,

Karkanias³

2003

Neuroendocrinology

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Diabetic female rats have decreased ovulation, reproductive behavior and luteinizing hormone surges. Peripheral insulin treatment restores the phenotype to normal and also corrects many of the metabolic changes. To further evaluate the role of insulin in the specific maintenance of reproductive behavior, rather than administering it peripherally, we gave insulin intracerebroventricularly (ICV) at doses that did not correct the peripheral metabolic changes associated with diabetes such as hyperglycemia. During the experiment, we assessed the general activity and reproductive behavior of gonadectomized, estrogen- and progesterone-treated diabetic and control, nondiabetic female rats. Some of the animals received ICV saline, the rest received ICV insulin. General activity (ambulation, rearing and corner sniffing) was not affected by any of the treatments. Streptozotocin-induced diabetes resulted in a significantly decreased lordosis quotient, and ICV insulin was able to completely prevent this reduction. Furthermore, ICV insulin was able to cause a modest increase in the lordosis quotient among nondiabetic rats as well. Moreover, ICV insulin also increased the quality of lordosis among diabetic rats. Our results support a central role of insulin in the control of reproductive functions, beyond maintaining the homeostatic and metabolic balance.

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Section: Discussionmentioning

confidence: 99%

Central Insulin Administration Maintains Reproductive Behavior in Diabetic Female Rats

Kovács

Morales²,

Karkanias³

2003

Neuroendocrinology

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“…Moreover, evidence exists that the number of central nervous insulin receptors are not down-regulated despite persistent hyperinsulinemia [75, 76]. Yet, the significance of insulin acting on brain functions in these patients in concert with the influence of microangiopathy, neuropathy, glycemic control and recurrent hypoglycemic events [16, 17, 18, 19, 20, 77]awaits further exploration.…”

Section: Discussionmentioning

confidence: 99%

“…Also patients with type 1 and type 2 diabetes can display hypo- or hyperinsulinemia. The potential impact of altered insulin concentrations in these patients during daily life on brain functions [16, 17, 18, 19], as well as on the development of hypoglycemia unawareness [20], is presently barely understood.…”

Section: Introductionmentioning

confidence: 99%

Improving Influence of Insulin on Cognitive Functions in Humans

Peters²,

et al. 2001

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Insulin receptors have been identified in limbic brain structures, but their functional relevance is still unclear. In order to characterize some of their effects, we evaluated auditory evoked brain potentials (AEP) in a vigilance task, behavioral measures of memory (recall of words) and selective attention (Stroop test) during infusion of insulin. The hormone was infused at two different rates (1.5 mU/kg × min, ‘low insulin’, and 15 mU/kg × min, ‘high insulin’), inducing respectively serum levels of 543 ± 34 and 24,029 ± 1,595 pmol/l. This experimental design allowed to compare cognitive parameters under two conditions presenting markedly different insulin levels, but with minimal incidence on blood glucose concentrations since these were kept constant by glucose infusion. A ‘no insulin treatment’ group was not included in order to avoid leaving patients infused with glucose without insulin treatment. Measures were taken during a baseline phase preceding insulin infusion and every 90 min during the 360 min of insulin infusion. Compared with ‘low insulin’, ‘high insulin’ induced a slow negative potential shift in the AEP over the frontal cortex (average amplitude, high insulin: 0.27 ± 0.48 µV; low insulin: 1.87 ± 0.48 µV, p < 0.005), which was paralleled by enhanced memory performance (words recalled, high insulin: 22.04 ± 0.93; low insulin: 19.29 ± 0.92, p < 0.05). Also, during ‘high insulin’ subjects displayed enhanced performance on the Stroop test (p < 0.05) and expressed less difficulty in thinking than during ‘low insulin’ (p < 0.03). Results indicate an improving effect of insulin on cognitive function, and may provide a frame for further investigations of neurobehavioral effects of insulin in patients with lowered or enhanced brain insulin, i.e., patients with Alzheimer’s disease or diabetes mellitus.

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“…The present data also suggest that the influence of the diabetes syndrome on age-related brain glucose utilization rate patterns resulted in an apparent suppression of brain carbohydrate utilization rates from ever achieving the normal development-associated levels demonstrated by 8- to 20-week-old controls. These data indicate that the diabetes mutation and/or associated syndrome factors suppress normal maturation-associated rates of neuronal glucose utilization from being realized [33]. The inability to maximize carbohydrate utilization in diabetics may compromise subsequent brain development or function from occurring, and predispose these CNS loci to the premature degenerative or dysfunctional changes described for several obese-diabetes species [2, 3, 5, 8, 12].…”

Section: Discussionmentioning

confidence: 99%

Estrogenic Stimulation of Hypothalamic-Limbic System Metabolism in Ageing Diabetic C57BL/KsJ Mice

Garris

1999

Neuroendocrinology

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The therapeutic influences of estrogen treatment on age- and diabetes-related declines in regional brain glucose utilization (RBGU) rates were evaluated in 8- to 20-week-old female C57BL/KsJ normal (+/?) and diabetic (db/db) mice. Following either oil vehicle (oil: 0.1 ml) or estradiol (E: 1 µg/3.5 days) treatments starting at 3 weeks of age, RBGU rates were subsequently determined at 8, 12, 16 and 20 weeks of age. A gradual decline in the basal rate of brain glucose utilization was observed in all control (oil- and E-treated) groups between 8 and 20 weeks. Expression of the hyperglycemic-obese diabetes syndrome in db/db mice resulted in a significant reduction in RBGU rates between 8 and 20 weeks relative to control values. In estrogen-sensitive hypothalamic, septal and amygdaloid regions, E therapy modulated RBGU rates in db/db mice relative to oil-treated diabetics, but did not significantly alter utilization rates in +/? mice. In cortical samples, E therapy had no significant influence on glucose utilization rates in either control or diabetic groups. A noticeable pattern of maturation-associated decline in CNS glucose utilization rates in all brain regions resulted in comparable regional metabolic indices being exhibited by all groups at 20 weeks of age, with the exception of the diabetes-associated exacerbation of RBGU rates in the oil-treated db/db group. These data demonstrate that the normal development-related decline in regional brain carbohydrate metabolism is accelerated by the diabetes syndrome, and that E therapy can modulate the syndrome-associated suppression of glucose utilization in steroid-sensitive CNS loci. These data suggest that the depressive influences of the diabetes syndrome on brain carbohydrate utilization rates may be therapeutically modified in recognized CNS regions possessing steroid-sequestering, metabolically responsive neurons.

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The Impact of Diabetes on the CNS

Cited by 254 publications

References 191 publications

Central Insulin Administration Maintains Reproductive Behavior in Diabetic Female Rats

Central Insulin Administration Maintains Reproductive Behavior in Diabetic Female Rats

Improving Influence of Insulin on Cognitive Functions in Humans

Estrogenic Stimulation of Hypothalamic-Limbic System Metabolism in Ageing Diabetic C57BL/KsJ Mice

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