Biomaterial Database

Glucagon responses of isolated α cells to glucose, insulin, somatostatin, and leptin. 2011

Lijun Chen, and Jacques Philippe, and Roger H Unger

Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

OBJECTIVE To determine whether glucagon suppression by leptin represents a direct effect on α cells rather than an indirect effect mediated via the hypothalamus. METHODS We devised an in vitro α-cell suppression assay in cultured hamster InR1G9 cells. InR1G9 hamster cells were infected with adenovirus containing mouse leptin receptors, and they were then incubated with leptin, insulin, or somatostatin in concentrations known to suppress glucagon in vivo. RESULTS Whereas somatostatin and insulin both suppressed the increase in glucagon secretion stimulated by high levels of glucose, leptin had no such effect. This inability of leptin to suppress glucagon in vitro could signify that it acts indirectly by causing the release of glucagon-suppressing peptides from the hypothalamus or stomach. To search for such a peptide, we studied the effects on glucagon secretion of 6 neuropeptides: orexin, melanocyte-stimulating hormone, neuropeptide Y, cocaine and amphetamine regulated transcript, neurotensin, and Agouti-related peptide that might be involved in the hypothalamic action of leptin. None of these peptides suppressed glucagon at low, normal, or elevated glucose concentrations. CONCLUSIONS If the cultured α cells used faithfully mimic the leptin response of in situ α cells of the diabetic animal, the glucagon-suppressing action of leptin is indirect, but is not mediated by any 1 of the 6 neuropeptides tested.

UI	MeSH Term	Description	Entries
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D005934	Glucagon	A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)	Glucagon (1-29),Glukagon,HG-Factor,Hyperglycemic-Glycogenolytic Factor,Proglucagon (33-61),HG Factor,Hyperglycemic Glycogenolytic Factor
D005947	Glucose	A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.	Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006224	Cricetinae	A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.	Cricetus,Hamsters,Hamster
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013004	Somatostatin	A 14-amino acid peptide named for its ability to inhibit pituitary GROWTH HORMONE release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of THYROID-STIMULATING HORMONE; PROLACTIN; INSULIN; and GLUCAGON besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, SRIF-28 with a 14-amino acid extension at the N-terminal.	Cyclic Somatostatin,Somatostatin-14,Somatotropin Release-Inhibiting Hormone,SRIH-14,Somatofalk,Somatostatin, Cyclic,Somatotropin Release-Inhibiting Factor,Stilamin,Somatostatin 14,Somatotropin Release Inhibiting Factor,Somatotropin Release Inhibiting Hormone
D050416	Glucagon-Secreting Cells	A type of pancreatic cell representing about 5-20% of the islet cells. Alpha cells secrete GLUCAGON.	Pancreatic alpha Cells,alpha Cells, Pancreatic,Pancreatic A Cells,Cell, Glucagon-Secreting,Cells, Glucagon-Secreting,Glucagon Secreting Cells,Glucagon-Secreting Cell,Pancreatic A Cell,Pancreatic alpha Cell,alpha Cell, Pancreatic
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D054411	Receptors, Leptin	Cell surface receptors for obesity factor (LEPTIN), a hormone secreted by the WHITE ADIPOCYTES. Upon leptin-receptor interaction, the signal is mediated through the JAK2/STAT3 pathway to regulate food intake, energy balance and fat storage.	Antigens, CD295,CD295 Antigens,Leptin Receptors,OB Receptor,LEPR Protein,Leptin Receptor,Leptin Receptor, Large Isoform,Leptin Receptor, Small Isoform,Leptin-Binding Protein,OBRa Receptor,OBRb Receptor,Receptor, Leptin,Leptin Binding Protein,Receptor, OB,Receptor, OBRa,Receptor, OBRb