Effects of amylin on glucose metabolism and glycogenolysis in vivo and in vitro.

Young, Douglas A.; Deems, Rhonda Oetting; Deacon, Richard; McIntosh, Raymond H; Foley, James E.

doi:10.1152/ajpendo.1990.259.3.e457

Cited by 49 publications

(52 citation statements)

References 17 publications

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“…This action of amylin may contribute to the increased muscle lactate production in vitro [7], increased glucose-6-phosphate concentration [17], and decreased total glycogen content [I73 following amylin stimulation. The appearance of lactate in the plasma following amylin administration in this study is consistent with amylin-induced muscle glycogenolysis.…”

Section: Resultsmentioning

confidence: 99%

Amylin injection causes elevated plasma lactate and glucose in the rat

Young¹,

Wang²,

Cooper³

1991

FEBS Letters

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Intravenous injections of 25.5 nmol rat amylin into fasted anesthetized rats caused a rapid increase in plasma lactate followed by an increase in plasma glucose; there was a transient fall in blood pressure. Subcutaneous injection of 25.5 nmol amylin also caused increases in lactate and glucose but did not change blood pressure. Similar responses were observed during somatostatin infusion and in the absence of changes in catecholamines. These results fit with a scheme in which amylin elicits muscle glycogenolysis, release of lactate, and increased hepatic gluconeogenesis due to increased supply of substrate.

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Section: Resultsmentioning

confidence: 99%

Amylin injection causes elevated plasma lactate and glucose in the rat

Young¹,

Wang²,

Cooper³

1991

FEBS Letters

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“…Cannulas were surgically implanted [36] into the jugular vein and carotid artery of overnight (18 h) fasted female mice anaesthetized with sodium pentobarbital (50 mg/kg). Animals remained anaesthetized for the duration of the study.…”

Section: Methodsmentioning

confidence: 99%

Expression of human GLUT4 in mice results in increased insulin action

Deems¹,

Evans²,

Deacon³

et al. 1994

Diabetologia

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Summary Glucose metabolism was evaluated in transgenic mice expressing the human GLUT 4 glucose transporter. Fed GLUT 4 transgenic mice exhibited a 32 % and 56 % reduction in serum glucose and insulin and a 69 % and 33 % increase in non-esterified fatty acid and lactate levels, respectively. Transgenic mice exhibited a significant increase in whole-body glucose disposal during a euglycaemic-hyperinsulinaemic clamp. Insulin-stin'mlated glucose uptake in isolated soleus muscles and adipocytes was greater in transgenic compared to control mice due to increased basal glucose uptake. Transgenic mice displayed increased glycogen levels in liver and gastrocnemius muscle, and increased insulin-stimulated 14C-glycogen accumulation in isolated soleus muscle. We conclude that over-expression of the GLUT 4 glucose transporter in mice results in 1) an increase in whole-body glucose disposal and storage, and 2) an increase in both basal and insulin-stimulated glucose uptake and disposal in vitro. These changes resulted in the reduction of serum glucose and insulin levels. These results provide direct evidence that glucose transport (and GLUT 4 per se) plays a significant role in regulating wholebody glucose homeostasis. Additionally, these data support the idea that pharmacological strategies directed at increasing the expression of GLUT 4 protein may have beneficial (hypoglycaemic) effects in the diabetic state. [Diabetologia (1994[Diabetologia ( ) 37: 1097[Diabetologia ( -1104

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“…IAPP was originally isolated from amyloid deposits in islets of Langerhans from non-insulin-dependent diabetic pancreas and insulinomas (2,3). It has since been shown to play a role in the normal regulation of glucose metabolism (4,5).…”

mentioning

confidence: 99%

Glucose Regulates Islet Amyloid Polypeptide Gene Transcription in a PDX1- and Calcium-dependent Manner

Macfarlane¹,

Campbell²,

Elrick³

et al. 2000

Journal of Biological Chemistry

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Islet amyloid polypeptide (IAPP) and insulin are expressed in the ␤-cells of the islets of Langerhans. They are co-secreted in response to changes in glucose concentration, and their mRNA levels are also regulated by glucose. The promoters of both genes share similar cisacting sequence elements, and both bind the homeodomain transcription factor PDX1, which plays an important role in the regulation of the insulin promoter and insulin mRNA levels by glucose. Here we examine the role of PDX1 in the regulation of the human IAPP promoter by glucose. The experiments were facilitated by the availability of a human ␤-cell line (NES2Y) that lacks PDX1. NES2Y cells also lack operational K ATP channels, resulting in a loss of control of calcium signaling. We have previously used these cells to show that glucose regulation of the insulin gene is dependent on PDX1, but not calcium. In the mouse ␤-cell line Min6, glucose (16 mM) stimulated a 3.5-4-fold increase in the activity of a ؊222 to ؉450 IAPP promoter construct compared with values observed in 0.5 mM glucose. In NES2Y cells, glucose failed to stimulate transcriptional activation of the IAPP promoter. Overexpression of PDX1 in NES2Y cells failed to reinstate glucose-responsive control of the IAPP promoter. Glucose effects on the IAPP promoter were observed only in the presence of PDX1 when normal calcium signaling was restored by overexpression of the two K ATP channel subunits SUR1 and Kir6.2. The importance of calcium was further emphasized by an experiment in which glucose-stimulated IAPP promoter activity was inhibited by the calcium channel blocker verapamil (50 M). Verapamil was further shown to inhibit the stimulatory effect of glucose on IAPP mRNA levels. These results demonstrate that like the insulin promoter, glucose regulation of the IAPP promoter is dependent on the activity of PDX1, but unlike the insulin promoter, it additionally requires the activity of another, as yet uncharacterized factor(s), the activity of which is calcium-dependent. Islet amyloid polypeptide (IAPP),1 also known as amylin, is a 37-amino acid peptide of the calcitonin gene family (1). IAPP was originally isolated from amyloid deposits in islets of Langerhans from non-insulin-dependent diabetic pancreas and insulinomas (2, 3). It has since been shown to play a role in the normal regulation of glucose metabolism (4, 5).IAPP and insulin are co-secreted in a regulated manner following stimulation with glucose and a variety of other secretagogues (6, 7). Transcription of the IAPP (8, 9) and insulin (10) genes is also stimulated by glucose. In the case of insulin, multiple cis-acting elements located within a relatively short region (Ϫ1 to Ϫ360) upstream of the start site contribute to the regulation of the gene by glucose and other nutrients (11). The homeodomain transcription factor PDX1 (12), which binds to a number of elements termed the A-boxes (13) within this region, plays a particularly important role (14,15). Recently, the cell signaling pathway linking glucose metabolism to the ...

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Effects of amylin on glucose metabolism and glycogenolysis in vivo and in vitro.

Cited by 49 publications

References 17 publications

Amylin injection causes elevated plasma lactate and glucose in the rat

Amylin injection causes elevated plasma lactate and glucose in the rat

Expression of human GLUT4 in mice results in increased insulin action

Glucose Regulates Islet Amyloid Polypeptide Gene Transcription in a PDX1- and Calcium-dependent Manner

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