Abstract
Type 2 diabetes mellitus results from a complex interaction between nutritional excess and multiple genes. Whereas pancreatic β-cells normally respond to glucose challenge by rapid insulin release (first phase insulin secretion), there is a loss of this acute response in virtually all of the type 2 diabetes patients with significant fasting hyperglycemia. Our previous studies demonstrated that irreversible intracellular accumulation of a glucose metabolite, protein O-linked N-acetylglucosamine modification (O-GlcNAc), is associated with pancreatic β-cell apoptosis. In the present study, we show that streptozotocin (STZ), a non-competitive chemical blocker of O-GlcNAcase, induces an insulin secretory defect in isolated rat islet cells. In contrast, transgenic mice with down-regulated glucose to glucosamine metabolism in β-cells exhibited an enhanced insulin secretion capacity. Interestingly, the STZ blockade of O-GlcNAcase activity is also associated with a growth hormone secretory defect and impairment of intracellular secretory vesicle trafficking. These results provide evidence for the roles of O-GlcNAc in the insulin secretion and possible involvement of O-GlcNAc in general glucose-regulated hormone secretion pathways.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 135-146 |
| Number of pages | 12 |
| Journal | Molecular and Cellular Endocrinology |
| Volume | 194 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Aug 30 2002 |
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Keywords
- Diabetes mellitus
- Glucose
- Insulin
- Pituitary
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Endocrinology
Cite this
Streptozotocin, an O-GlcNAcase inhibitor, blunts insulin and growth hormone secretion. / Liu, Kan; Paterson, Andrew J.; Konrad, Robert J.; Parlow, A. F.; Jimi, Shiro; Roh, Meejeon; Chin, Edward; Kudlow, Jeffrey E.
In: Molecular and Cellular Endocrinology, Vol. 194, No. 1-2, 30.08.2002, p. 135-146.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Streptozotocin, an O-GlcNAcase inhibitor, blunts insulin and growth hormone secretion
AU - Liu, Kan
AU - Paterson, Andrew J.
AU - Konrad, Robert J.
AU - Parlow, A. F.
AU - Jimi, Shiro
AU - Roh, Meejeon
AU - Chin, Edward
AU - Kudlow, Jeffrey E.
PY - 2002/8/30
Y1 - 2002/8/30
N2 - Type 2 diabetes mellitus results from a complex interaction between nutritional excess and multiple genes. Whereas pancreatic β-cells normally respond to glucose challenge by rapid insulin release (first phase insulin secretion), there is a loss of this acute response in virtually all of the type 2 diabetes patients with significant fasting hyperglycemia. Our previous studies demonstrated that irreversible intracellular accumulation of a glucose metabolite, protein O-linked N-acetylglucosamine modification (O-GlcNAc), is associated with pancreatic β-cell apoptosis. In the present study, we show that streptozotocin (STZ), a non-competitive chemical blocker of O-GlcNAcase, induces an insulin secretory defect in isolated rat islet cells. In contrast, transgenic mice with down-regulated glucose to glucosamine metabolism in β-cells exhibited an enhanced insulin secretion capacity. Interestingly, the STZ blockade of O-GlcNAcase activity is also associated with a growth hormone secretory defect and impairment of intracellular secretory vesicle trafficking. These results provide evidence for the roles of O-GlcNAc in the insulin secretion and possible involvement of O-GlcNAc in general glucose-regulated hormone secretion pathways.
AB - Type 2 diabetes mellitus results from a complex interaction between nutritional excess and multiple genes. Whereas pancreatic β-cells normally respond to glucose challenge by rapid insulin release (first phase insulin secretion), there is a loss of this acute response in virtually all of the type 2 diabetes patients with significant fasting hyperglycemia. Our previous studies demonstrated that irreversible intracellular accumulation of a glucose metabolite, protein O-linked N-acetylglucosamine modification (O-GlcNAc), is associated with pancreatic β-cell apoptosis. In the present study, we show that streptozotocin (STZ), a non-competitive chemical blocker of O-GlcNAcase, induces an insulin secretory defect in isolated rat islet cells. In contrast, transgenic mice with down-regulated glucose to glucosamine metabolism in β-cells exhibited an enhanced insulin secretion capacity. Interestingly, the STZ blockade of O-GlcNAcase activity is also associated with a growth hormone secretory defect and impairment of intracellular secretory vesicle trafficking. These results provide evidence for the roles of O-GlcNAc in the insulin secretion and possible involvement of O-GlcNAc in general glucose-regulated hormone secretion pathways.
KW - Diabetes mellitus
KW - Glucose
KW - Insulin
KW - Pituitary
UR - http://www.scopus.com/inward/record.url?scp=0037200680&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037200680&partnerID=8YFLogxK
U2 - 10.1016/S0303-7207(02)00155-7
DO - 10.1016/S0303-7207(02)00155-7
M3 - Article
C2 - 12242036
AN - SCOPUS:0037200680
VL - 194
SP - 135
EP - 146
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
IS - 1-2
ER -