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β-Amyloid-induced cognitive dysfunction impairs glucose homeostasis by increasing insulin resistance and decreasing β-cell mass in non-diabetic and diabetic rats.
Metabolism 2013; 62(12):1749-60M

Abstract

OBJECTIVE

β-Amyloid accumulation in the brain may impair glucose homeostasis in both the brain and peripheral tissues. The present study investigated whether β-amyloid deposition in the hippocampus impairs glucose homeostasis by altering insulin sensitivity, glucose-stimulated insulin secretion or β-cell mass.

METHODS

Male rats were divided into two groups: a non-diabetic sham group and a diabetic partial pancreatectomized (Px) group. Each group was then subdivided into three treatment groups that received intra-CA1 infusions of β-amyloid (25-35; AMY), β-amyloid (35-25; RAMY; non-plaque forming), or saline at a rate of 3.6 nmol/day for 14 days.

RESULTS

After 4weeks, cognitive function measured by passive avoidance and water maze tests was impaired in non-diabetic rats that received AMY compared with rats that received saline or RAMY. Furthermore, diabetes exacerbated cognitive dysfunction in AMY-infused rats. This was associated with the hyperphosphorylation of tau as a result of attenuated insulin signaling (pAkt→pGSK) through decreased phosphorylation of cAMP responding element binding protein in the hippocampus of non-diabetic and diabetic rats. AMY exacerbated whole-body and hepatic insulin resistance in non-diabetic and diabetic rats. However, AMY potentiated glucose-stimulated insulin secretion in non-diabetic and diabetic rats, but caused decreased β-cell mass via increased β-cell apoptosis and decreased β-cell proliferation. As a result, glucose homeostasis was maintained by potentiating insulin secretion in diabetic rats, but may not be sustainable with further decreases in β-cell mass.

CONCLUSION

Cognitive dysfunction attributable to β-amyloid accumulation in the hippocampus might be related to disturbed glucose homeostasis due to increased insulin resistance and decreased β-cell mass.

Authors+Show Affiliations

Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan, Korea. Electronic address: smpark@hoseo.edu.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24050268

Citation

Park, Sunmin, et al. "Β-Amyloid-induced Cognitive Dysfunction Impairs Glucose Homeostasis By Increasing Insulin Resistance and Decreasing Β-cell Mass in Non-diabetic and Diabetic Rats." Metabolism: Clinical and Experimental, vol. 62, no. 12, 2013, pp. 1749-60.
Park S, Kim DS, Kang S, et al. Β-Amyloid-induced cognitive dysfunction impairs glucose homeostasis by increasing insulin resistance and decreasing β-cell mass in non-diabetic and diabetic rats. Metab Clin Exp. 2013;62(12):1749-60.
Park, S., Kim, D. S., Kang, S., & Moon, N. R. (2013). Β-Amyloid-induced cognitive dysfunction impairs glucose homeostasis by increasing insulin resistance and decreasing β-cell mass in non-diabetic and diabetic rats. Metabolism: Clinical and Experimental, 62(12), pp. 1749-60. doi:10.1016/j.metabol.2013.08.007.
Park S, et al. Β-Amyloid-induced Cognitive Dysfunction Impairs Glucose Homeostasis By Increasing Insulin Resistance and Decreasing Β-cell Mass in Non-diabetic and Diabetic Rats. Metab Clin Exp. 2013;62(12):1749-60. PubMed PMID: 24050268.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - β-Amyloid-induced cognitive dysfunction impairs glucose homeostasis by increasing insulin resistance and decreasing β-cell mass in non-diabetic and diabetic rats. AU - Park,Sunmin, AU - Kim,Da Sol, AU - Kang,Suna, AU - Moon,Na Rang, Y1 - 2013/09/16/ PY - 2013/05/14/received PY - 2013/08/13/revised PY - 2013/08/13/accepted PY - 2013/9/21/entrez PY - 2013/9/21/pubmed PY - 2014/1/9/medline KW - 5-bromo-2-deoxyuridine KW - AMY KW - BrdU KW - CREB KW - Cognitive dysfunction KW - GSK KW - HOMA-IR KW - Homeostatic model assessment for insulin resistance. KW - Insulin resistance KW - Insulin secretion KW - PKB or Akt KW - Px KW - RAMY KW - Sham KW - cAMP responding element binding protein KW - glycogen synthase kinase KW - partial pancreatectomy KW - protein kinase B KW - sham-operation KW - β-amyloid KW - β-amyloid (25–35) KW - β-amyloid (35–25) KW - β-cell apoptosis SP - 1749 EP - 60 JF - Metabolism: clinical and experimental JO - Metab. Clin. Exp. VL - 62 IS - 12 N2 - OBJECTIVE: β-Amyloid accumulation in the brain may impair glucose homeostasis in both the brain and peripheral tissues. The present study investigated whether β-amyloid deposition in the hippocampus impairs glucose homeostasis by altering insulin sensitivity, glucose-stimulated insulin secretion or β-cell mass. METHODS: Male rats were divided into two groups: a non-diabetic sham group and a diabetic partial pancreatectomized (Px) group. Each group was then subdivided into three treatment groups that received intra-CA1 infusions of β-amyloid (25-35; AMY), β-amyloid (35-25; RAMY; non-plaque forming), or saline at a rate of 3.6 nmol/day for 14 days. RESULTS: After 4weeks, cognitive function measured by passive avoidance and water maze tests was impaired in non-diabetic rats that received AMY compared with rats that received saline or RAMY. Furthermore, diabetes exacerbated cognitive dysfunction in AMY-infused rats. This was associated with the hyperphosphorylation of tau as a result of attenuated insulin signaling (pAkt→pGSK) through decreased phosphorylation of cAMP responding element binding protein in the hippocampus of non-diabetic and diabetic rats. AMY exacerbated whole-body and hepatic insulin resistance in non-diabetic and diabetic rats. However, AMY potentiated glucose-stimulated insulin secretion in non-diabetic and diabetic rats, but caused decreased β-cell mass via increased β-cell apoptosis and decreased β-cell proliferation. As a result, glucose homeostasis was maintained by potentiating insulin secretion in diabetic rats, but may not be sustainable with further decreases in β-cell mass. CONCLUSION: Cognitive dysfunction attributable to β-amyloid accumulation in the hippocampus might be related to disturbed glucose homeostasis due to increased insulin resistance and decreased β-cell mass. SN - 1532-8600 UR - https://www.unboundmedicine.com/medline/citation/24050268/β_Amyloid_induced_cognitive_dysfunction_impairs_glucose_homeostasis_by_increasing_insulin_resistance_and_decreasing_β_cell_mass_in_non_diabetic_and_diabetic_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0026-0495(13)00256-4 DB - PRIME DP - Unbound Medicine ER -