Characterization of glucagon-like peptide-1-(7-36)amide in the hypothalamus.
The distribution of glucagon-like peptide-1-(7-36)amide like immunoreactivity (GLP-1-(7-36)NH2 IR) in rat brain was determined. Highest concentrations were found in the hypothalamus. A combination of gel chromatography and anion exchange chromatography showed that the majority of hypothalamic immunoreactivity exactly corresponded in position to synthetic GLP-1-(7-36)NH2. Chromatographic analyses of rat ileum demonstrated a similar pattern, whereas in rat pancreas mainly a large proglucagon fragment and GLP-1 were indicated. Determination of the subcellular distribution by differential centrifugation of hypothalamic tissue revealed that most of the GLP-1-(7-36)NH2 IR was present in the synaptosome fraction. GLP-1-(7-36)NH2 was released from hypothalamic tissue slices in a calcium-dependent fashion by potassium-induced depolarization. Thus GLP-1-(7-36)NH2 appears to fulfil two criteria for a neurotransmitter. No change was found in its hypothalamic content in streptozocin-induced diabetic rats compared to normal controls but a decrease was seen in hyperinsulinemic hyperglycemic KKAy mice compared to KK mice.
Kreymann
B
B
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
Ghatei
M A
MA
Burnet
P
P
Williams
G
G
Kanse
S
S
Diani
A R
AR
Bloom
S R
SR
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007031:Hypothalamus / Q000378:metabolism*; D007150:Immunohistochemistry; D010446:Peptide Fragments; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D010446:Peptide Fragments; D010455:Peptides; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon