Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats
Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats. P J Havel , T M Hahn , D K Sindelar , D G Baskin , M F Dallman , D S Weigle and M W Schwartz Department of Nutrition, University of California,...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2000-02, Vol.49 (2), p.244-252 |
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| creator | HAVEL, P. J HAHN, T. M SINDELAR, D. K BASKIN, D. G DALLMAN, M. F WEIGLE, D. S SCHWARTZ, M. W |
| description | Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling
protein 3 expression in rats.
P J Havel ,
T M Hahn ,
D K Sindelar ,
D G Baskin ,
M F Dallman ,
D S Weigle and
M W Schwartz
Department of Nutrition, University of California, Davis 95616, USA. pjhavel@ucdavis.edu
Abstract
Hypothalamic melanocortins are among several neuropeptides strongly implicated in the control of food intake. Agonists for
melanocortin 4 (MC-4) receptors such as alpha-melanocyte-stimulating hormone (alpha-MSH), a product of proopiomelanocortin
(POMC), reduce food intake, whereas hypothalamic agouti-related protein (AgRP) is a MC-4 receptor antagonist that increases
food intake. To investigate whether reduced melanocortin signaling contributes to hyperphagia induced by uncontrolled diabetes,
male Sprague-Dawley rats were studied 7 days after administration of streptozotocin (STZ) or vehicle. In addition, we wished
to determine the effect of diabetes on muscle uncoupling protein 3 (UCP-3), a potential regulator of muscle energy metabolism.
STZ diabetic rats were markedly hyperglycemic (31.3 +/- 1.0 mmol/l; P < 0.005) compared with nondiabetic controls (9.3 +/-
0.2 mmol/l). Insulin treatment partially corrected the hyperglycemia (18.8 +/- 2.5 mol/l; P < 0.005). Plasma leptin was markedly
reduced in STZ diabetic rats (0.4 +/- 0.1 ng/ml; P < 0.005) compared with controls (3.0 +/- 0.4 ng/ml), an effect that was
also partially reversed by insulin treatment (1.8 +/- 0.3 ng/ml). Untreated diabetic rats were hyperphagic, consuming 40%
more food (48 +/- 1 g/day; P < 0.005) than controls (34 +/- 1 g/day). Hyperphagia was prevented by insulin treatment (32 +/-
2 g/day). In untreated diabetic rats, hypothalamic POMC mRNA expression (measured by in situ hybridization) was reduced by
80% (P < 0.005), whereas AgRP mRNA levels were increased by 60% (P < 0.01), suggesting a marked decrease of hypothalamic melanocortin
signaling. The change in POMC, but not in AgRP, mRNA levels was partially reversed by insulin treatment. By comparison, the
effects of diabetes to increase hypothalamic neuropeptide Y (NPY) expression and to decrease corticotropin-releasing hormone
(CRH) expression were normalized by insulin treatment, whereas the expression of mRNA encoding the long form of the leptin
receptor in the arcuate nucleus was unaltered by diabetes or insulin treatment. UCP-3 mRNA expression in gastrocnemius muscle
from diabetic rats was in |
| doi_str_mv | 10.2337/diabetes.49.2.244 |
| format | Article |
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protein 3 expression in rats.
P J Havel ,
T M Hahn ,
D K Sindelar ,
D G Baskin ,
M F Dallman ,
D S Weigle and
M W Schwartz
Department of Nutrition, University of California, Davis 95616, USA. pjhavel@ucdavis.edu
Abstract
Hypothalamic melanocortins are among several neuropeptides strongly implicated in the control of food intake. Agonists for
melanocortin 4 (MC-4) receptors such as alpha-melanocyte-stimulating hormone (alpha-MSH), a product of proopiomelanocortin
(POMC), reduce food intake, whereas hypothalamic agouti-related protein (AgRP) is a MC-4 receptor antagonist that increases
food intake. To investigate whether reduced melanocortin signaling contributes to hyperphagia induced by uncontrolled diabetes,
male Sprague-Dawley rats were studied 7 days after administration of streptozotocin (STZ) or vehicle. In addition, we wished
to determine the effect of diabetes on muscle uncoupling protein 3 (UCP-3), a potential regulator of muscle energy metabolism.
STZ diabetic rats were markedly hyperglycemic (31.3 +/- 1.0 mmol/l; P < 0.005) compared with nondiabetic controls (9.3 +/-
0.2 mmol/l). Insulin treatment partially corrected the hyperglycemia (18.8 +/- 2.5 mol/l; P < 0.005). Plasma leptin was markedly
reduced in STZ diabetic rats (0.4 +/- 0.1 ng/ml; P < 0.005) compared with controls (3.0 +/- 0.4 ng/ml), an effect that was
also partially reversed by insulin treatment (1.8 +/- 0.3 ng/ml). Untreated diabetic rats were hyperphagic, consuming 40%
more food (48 +/- 1 g/day; P < 0.005) than controls (34 +/- 1 g/day). Hyperphagia was prevented by insulin treatment (32 +/-
2 g/day). In untreated diabetic rats, hypothalamic POMC mRNA expression (measured by in situ hybridization) was reduced by
80% (P < 0.005), whereas AgRP mRNA levels were increased by 60% (P < 0.01), suggesting a marked decrease of hypothalamic melanocortin
signaling. The change in POMC, but not in AgRP, mRNA levels was partially reversed by insulin treatment. By comparison, the
effects of diabetes to increase hypothalamic neuropeptide Y (NPY) expression and to decrease corticotropin-releasing hormone
(CRH) expression were normalized by insulin treatment, whereas the expression of mRNA encoding the long form of the leptin
receptor in the arcuate nucleus was unaltered by diabetes or insulin treatment. UCP-3 mRNA expression in gastrocnemius muscle
from diabetic rats was increased fourfold (P < 0.005), and the increase was prevented by insulin treatment. The effect of
uncontrolled diabetes to decrease POMC, while increasing AgRP gene expression, suggests that reduced hypothalamic melanocortin
signaling, along with increased NPY and decreased CRH signaling, could contribute to diabetic hyperphagia. These responses,
in concert with increased muscle UCP-3 expression, may also contribute to the catabolic effects of uncontrolled diabetes on
fuel metabolism in peripheral tissues.]]></description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/diabetes.49.2.244</identifier><identifier>PMID: 10868941</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Animals ; Appetite ; Appetite (Psychophysiology) ; Biological and medical sciences ; Body fat ; Body Weight - drug effects ; Carrier Proteins - metabolism ; Diabetes ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Experimental - pathology ; Diabetes Mellitus, Experimental - physiopathology ; Diabetes research ; Diabetes. Impaired glucose tolerance ; Eating - drug effects ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Energy ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Fasting ; Food ; Gene expression ; Homeostasis ; Hormones ; Hormones - blood ; Hypothalamus - metabolism ; Insulin ; Insulin - therapeutic use ; Ion Channels ; Male ; Medical sciences ; Metabolism ; Mitochondrial Proteins ; Muscle Proteins - metabolism ; Musculoskeletal system ; Nervous system ; Neuropeptide Y - metabolism ; Neuropeptides ; Pathogenesis ; Peptide regulatory factors ; Physiological aspects ; Pro-Opiomelanocortin - metabolism ; Proteins ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; Receptors, Leptin ; Uncoupling Protein 3</subject><ispartof>Diabetes (New York, N.Y.), 2000-02, Vol.49 (2), p.244-252</ispartof><rights>2000 INIST-CNRS</rights><rights>COPYRIGHT 2000 American Diabetes Association</rights><rights>COPYRIGHT 2000 American Diabetes Association</rights><rights>Copyright American Diabetes Association Feb 2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c642t-50879e6da521c067b26f5ad8df0b73567f56fe2d4d5fa2847d643ea4e260aa2e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1362985$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10868941$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HAVEL, P. J</creatorcontrib><creatorcontrib>HAHN, T. M</creatorcontrib><creatorcontrib>SINDELAR, D. K</creatorcontrib><creatorcontrib>BASKIN, D. G</creatorcontrib><creatorcontrib>DALLMAN, M. F</creatorcontrib><creatorcontrib>WEIGLE, D. S</creatorcontrib><creatorcontrib>SCHWARTZ, M. W</creatorcontrib><title>Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description><![CDATA[Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling
protein 3 expression in rats.
P J Havel ,
T M Hahn ,
D K Sindelar ,
D G Baskin ,
M F Dallman ,
D S Weigle and
M W Schwartz
Department of Nutrition, University of California, Davis 95616, USA. pjhavel@ucdavis.edu
Abstract
Hypothalamic melanocortins are among several neuropeptides strongly implicated in the control of food intake. Agonists for
melanocortin 4 (MC-4) receptors such as alpha-melanocyte-stimulating hormone (alpha-MSH), a product of proopiomelanocortin
(POMC), reduce food intake, whereas hypothalamic agouti-related protein (AgRP) is a MC-4 receptor antagonist that increases
food intake. To investigate whether reduced melanocortin signaling contributes to hyperphagia induced by uncontrolled diabetes,
male Sprague-Dawley rats were studied 7 days after administration of streptozotocin (STZ) or vehicle. In addition, we wished
to determine the effect of diabetes on muscle uncoupling protein 3 (UCP-3), a potential regulator of muscle energy metabolism.
STZ diabetic rats were markedly hyperglycemic (31.3 +/- 1.0 mmol/l; P < 0.005) compared with nondiabetic controls (9.3 +/-
0.2 mmol/l). Insulin treatment partially corrected the hyperglycemia (18.8 +/- 2.5 mol/l; P < 0.005). Plasma leptin was markedly
reduced in STZ diabetic rats (0.4 +/- 0.1 ng/ml; P < 0.005) compared with controls (3.0 +/- 0.4 ng/ml), an effect that was
also partially reversed by insulin treatment (1.8 +/- 0.3 ng/ml). Untreated diabetic rats were hyperphagic, consuming 40%
more food (48 +/- 1 g/day; P < 0.005) than controls (34 +/- 1 g/day). Hyperphagia was prevented by insulin treatment (32 +/-
2 g/day). In untreated diabetic rats, hypothalamic POMC mRNA expression (measured by in situ hybridization) was reduced by
80% (P < 0.005), whereas AgRP mRNA levels were increased by 60% (P < 0.01), suggesting a marked decrease of hypothalamic melanocortin
signaling. The change in POMC, but not in AgRP, mRNA levels was partially reversed by insulin treatment. By comparison, the
effects of diabetes to increase hypothalamic neuropeptide Y (NPY) expression and to decrease corticotropin-releasing hormone
(CRH) expression were normalized by insulin treatment, whereas the expression of mRNA encoding the long form of the leptin
receptor in the arcuate nucleus was unaltered by diabetes or insulin treatment. UCP-3 mRNA expression in gastrocnemius muscle
from diabetic rats was increased fourfold (P < 0.005), and the increase was prevented by insulin treatment. The effect of
uncontrolled diabetes to decrease POMC, while increasing AgRP gene expression, suggests that reduced hypothalamic melanocortin
signaling, along with increased NPY and decreased CRH signaling, could contribute to diabetic hyperphagia. These responses,
in concert with increased muscle UCP-3 expression, may also contribute to the catabolic effects of uncontrolled diabetes on
fuel metabolism in peripheral tissues.]]></description><subject>Animals</subject><subject>Appetite</subject><subject>Appetite (Psychophysiology)</subject><subject>Biological and medical sciences</subject><subject>Body fat</subject><subject>Body Weight - drug effects</subject><subject>Carrier Proteins - metabolism</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>Diabetes Mellitus, Experimental - physiopathology</subject><subject>Diabetes research</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Eating - drug effects</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Energy</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Fasting</subject><subject>Food</subject><subject>Gene expression</subject><subject>Homeostasis</subject><subject>Hormones</subject><subject>Hormones - blood</subject><subject>Hypothalamus - metabolism</subject><subject>Insulin</subject><subject>Insulin - therapeutic use</subject><subject>Ion Channels</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolism</subject><subject>Mitochondrial Proteins</subject><subject>Muscle Proteins - metabolism</subject><subject>Musculoskeletal system</subject><subject>Nervous system</subject><subject>Neuropeptide Y - metabolism</subject><subject>Neuropeptides</subject><subject>Pathogenesis</subject><subject>Peptide regulatory factors</subject><subject>Physiological aspects</subject><subject>Pro-Opiomelanocortin - metabolism</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Cell Surface</subject><subject>Receptors, Leptin</subject><subject>Uncoupling Protein 3</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpt0lFrFDEQAOBFFFurP8AXCSIi0j2TbDa7-1iOWoWDvij4FnLJZC9lN1mTLO35V_yzRu9KPT3yEBK-mUmGKYqXBC9oVTUftJVrSBAXrFvQBWXsUXFKuqorK9p8e1ycYkxoSZquOSmexXiDMeZ5PS1OCG552zFyWvy8NAZUisgbFFOAKfkfPnllXWmdnhVodF8FSaeRdXEerEOZyjSCS8jnwwbQZjv5tJGDHK1CIwzSeeVDyjRuY4LxT_Q4RzUAmp3y85TT9GgKPkFGFYK7KUCMNufL5yBTfF48MXKI8GK_nxVfP15-WX4qV9dXn5cXq1JxRlNZ47bpgGtZU6Iwb9aUm1rqVhu8bqqaN6bmBqhmujaStqzRnFUgGVCOpaRQnRVvd3nzY77PEJMYbVQw5D-An6NoCCU1a6oMX_8Db_wcXH6boISzjtWsy-h8h3o5gLDO-BSk6sFBkIN3YGy-vqg71tY15pmXR3heGnInj_l3Bz6TBHepl3OMor1aHdDzY1T5YYAeRO7h8vqAkx1XwccYwIgp2FGGrSBY_J43cT8JgnWCijxvOebVviPzegT9V8RuwDJ4swcyKjmYIJ2y8cFVnHZtndn7HdvYfnNrAzzU-r_oLy2o8LM</recordid><startdate>20000201</startdate><enddate>20000201</enddate><creator>HAVEL, P. J</creator><creator>HAHN, T. M</creator><creator>SINDELAR, D. K</creator><creator>BASKIN, D. G</creator><creator>DALLMAN, M. F</creator><creator>WEIGLE, D. S</creator><creator>SCHWARTZ, M. W</creator><general>American Diabetes Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8GL</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20000201</creationdate><title>Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats</title><author>HAVEL, P. J ; HAHN, T. M ; SINDELAR, D. K ; BASKIN, D. G ; DALLMAN, M. F ; WEIGLE, D. S ; SCHWARTZ, M. W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c642t-50879e6da521c067b26f5ad8df0b73567f56fe2d4d5fa2847d643ea4e260aa2e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Appetite</topic><topic>Appetite (Psychophysiology)</topic><topic>Biological and medical sciences</topic><topic>Body fat</topic><topic>Body Weight - drug effects</topic><topic>Carrier Proteins - metabolism</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Experimental - pathology</topic><topic>Diabetes Mellitus, Experimental - physiopathology</topic><topic>Diabetes research</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Eating - drug effects</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Energy</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Fasting</topic><topic>Food</topic><topic>Gene expression</topic><topic>Homeostasis</topic><topic>Hormones</topic><topic>Hormones - blood</topic><topic>Hypothalamus - metabolism</topic><topic>Insulin</topic><topic>Insulin - therapeutic use</topic><topic>Ion Channels</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolism</topic><topic>Mitochondrial Proteins</topic><topic>Muscle Proteins - metabolism</topic><topic>Musculoskeletal system</topic><topic>Nervous system</topic><topic>Neuropeptide Y - metabolism</topic><topic>Neuropeptides</topic><topic>Pathogenesis</topic><topic>Peptide regulatory factors</topic><topic>Physiological aspects</topic><topic>Pro-Opiomelanocortin - metabolism</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Cell Surface</topic><topic>Receptors, Leptin</topic><topic>Uncoupling Protein 3</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HAVEL, P. J</creatorcontrib><creatorcontrib>HAHN, T. M</creatorcontrib><creatorcontrib>SINDELAR, D. K</creatorcontrib><creatorcontrib>BASKIN, D. G</creatorcontrib><creatorcontrib>DALLMAN, M. F</creatorcontrib><creatorcontrib>WEIGLE, D. S</creatorcontrib><creatorcontrib>SCHWARTZ, M. 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J</au><au>HAHN, T. M</au><au>SINDELAR, D. K</au><au>BASKIN, D. G</au><au>DALLMAN, M. F</au><au>WEIGLE, D. S</au><au>SCHWARTZ, M. W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2000-02-01</date><risdate>2000</risdate><volume>49</volume><issue>2</issue><spage>244</spage><epage>252</epage><pages>244-252</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract><![CDATA[Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling
protein 3 expression in rats.
P J Havel ,
T M Hahn ,
D K Sindelar ,
D G Baskin ,
M F Dallman ,
D S Weigle and
M W Schwartz
Department of Nutrition, University of California, Davis 95616, USA. pjhavel@ucdavis.edu
Abstract
Hypothalamic melanocortins are among several neuropeptides strongly implicated in the control of food intake. Agonists for
melanocortin 4 (MC-4) receptors such as alpha-melanocyte-stimulating hormone (alpha-MSH), a product of proopiomelanocortin
(POMC), reduce food intake, whereas hypothalamic agouti-related protein (AgRP) is a MC-4 receptor antagonist that increases
food intake. To investigate whether reduced melanocortin signaling contributes to hyperphagia induced by uncontrolled diabetes,
male Sprague-Dawley rats were studied 7 days after administration of streptozotocin (STZ) or vehicle. In addition, we wished
to determine the effect of diabetes on muscle uncoupling protein 3 (UCP-3), a potential regulator of muscle energy metabolism.
STZ diabetic rats were markedly hyperglycemic (31.3 +/- 1.0 mmol/l; P < 0.005) compared with nondiabetic controls (9.3 +/-
0.2 mmol/l). Insulin treatment partially corrected the hyperglycemia (18.8 +/- 2.5 mol/l; P < 0.005). Plasma leptin was markedly
reduced in STZ diabetic rats (0.4 +/- 0.1 ng/ml; P < 0.005) compared with controls (3.0 +/- 0.4 ng/ml), an effect that was
also partially reversed by insulin treatment (1.8 +/- 0.3 ng/ml). Untreated diabetic rats were hyperphagic, consuming 40%
more food (48 +/- 1 g/day; P < 0.005) than controls (34 +/- 1 g/day). Hyperphagia was prevented by insulin treatment (32 +/-
2 g/day). In untreated diabetic rats, hypothalamic POMC mRNA expression (measured by in situ hybridization) was reduced by
80% (P < 0.005), whereas AgRP mRNA levels were increased by 60% (P < 0.01), suggesting a marked decrease of hypothalamic melanocortin
signaling. The change in POMC, but not in AgRP, mRNA levels was partially reversed by insulin treatment. By comparison, the
effects of diabetes to increase hypothalamic neuropeptide Y (NPY) expression and to decrease corticotropin-releasing hormone
(CRH) expression were normalized by insulin treatment, whereas the expression of mRNA encoding the long form of the leptin
receptor in the arcuate nucleus was unaltered by diabetes or insulin treatment. UCP-3 mRNA expression in gastrocnemius muscle
from diabetic rats was increased fourfold (P < 0.005), and the increase was prevented by insulin treatment. The effect of
uncontrolled diabetes to decrease POMC, while increasing AgRP gene expression, suggests that reduced hypothalamic melanocortin
signaling, along with increased NPY and decreased CRH signaling, could contribute to diabetic hyperphagia. These responses,
in concert with increased muscle UCP-3 expression, may also contribute to the catabolic effects of uncontrolled diabetes on
fuel metabolism in peripheral tissues.]]></abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>10868941</pmid><doi>10.2337/diabetes.49.2.244</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-1797 |
| ispartof | Diabetes (New York, N.Y.), 2000-02, Vol.49 (2), p.244-252 |
| issn | 0012-1797 1939-327X |
| language | eng |
| recordid | cdi_pubmed_primary_10868941 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Appetite Appetite (Psychophysiology) Biological and medical sciences Body fat Body Weight - drug effects Carrier Proteins - metabolism Diabetes Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Experimental - pathology Diabetes Mellitus, Experimental - physiopathology Diabetes research Diabetes. Impaired glucose tolerance Eating - drug effects Endocrine pancreas. Apud cells (diseases) Endocrinopathies Energy Etiopathogenesis. Screening. Investigations. Target tissue resistance Fasting Food Gene expression Homeostasis Hormones Hormones - blood Hypothalamus - metabolism Insulin Insulin - therapeutic use Ion Channels Male Medical sciences Metabolism Mitochondrial Proteins Muscle Proteins - metabolism Musculoskeletal system Nervous system Neuropeptide Y - metabolism Neuropeptides Pathogenesis Peptide regulatory factors Physiological aspects Pro-Opiomelanocortin - metabolism Proteins Rats Rats, Sprague-Dawley Receptors, Cell Surface Receptors, Leptin Uncoupling Protein 3 |
| title | Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T00%3A10%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effects%20of%20streptozotocin-induced%20diabetes%20and%20insulin%20treatment%20on%20the%20hypothalamic%20melanocortin%20system%20and%20muscle%20uncoupling%20protein%203%20expression%20in%20rats&rft.jtitle=Diabetes%20(New%20York,%20N.Y.)&rft.au=HAVEL,%20P.%20J&rft.date=2000-02-01&rft.volume=49&rft.issue=2&rft.spage=244&rft.epage=252&rft.pages=244-252&rft.issn=0012-1797&rft.eissn=1939-327X&rft.coden=DIAEAZ&rft_id=info:doi/10.2337/diabetes.49.2.244&rft_dat=%3Cgale_pubme%3EA59485506%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=216494549&rft_id=info:pmid/10868941&rft_galeid=A59485506&rfr_iscdi=true |