What Regulates Basal Insulin Secretion and Causes Hyperinsulinemia?

Diabetes ◽  
2021 ◽  
Vol 70 (10) ◽  
pp. 2174-2182
Author(s):  
Barbara E. Corkey ◽  
Jude T. Deeney ◽  
Matthew J. Merrins
Keyword(s):  
Insulin Secretion ◽  
Basal Insulin ◽  
Basal Insulin Secretion

Effect of fatty acids on insulin release: role of chain length and degree of unsaturation

1994 ◽  
Vol 266 (4) ◽  
pp. E635-E639 ◽  
Author(s):  
E. C. Opara ◽  
M. Garfinkel ◽  
V. S. Hubbard ◽  
W. M. Burch ◽  
O. E. Akwari
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Fatty Acid ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Basal Insulin ◽  
Degree Of Unsaturation ◽  
Structural Differences ◽  
Basal Insulin Secretion

The purpose of the present study was to examine the role played by structural differences among fatty acids in their effect on insulin secretion by isolated perifused murine islets. Insulin secretion measured by radioimmunoassay was assessed either as total insulin output (ng.6 islets-1.20 min-1) or as percent of basal insulin secretion. Raising the glucose concentration from a basal 5.5 to 27.7 mM caused an increase of insulin output from 6.69 +/- 1.59 to 19.92 +/- 4.99 ng.6 islets-1.20 min-1 (P < 0.05) in control (untreated) islets. However, after 20-min exposure of islets to 5 mM 16:0 or 18:2, the effect of 27.7 mM glucose was enhanced or diminished, respectively. Basal insulin output (100% basal) changed to 44 +/- 10% basal (P < 0.005) with the addition of 5 mM 4:0 but was not altered when 4:0 was replaced by 6:0. Insulin output increased modestly with 5 mM 8:0 but significantly (P < 0.05) with 10:0 until a maximal of 280 +/- 24% basal with 12:0 (P < 0.01), then fell to 110 +/- 18 and 93 +/- 15% basal (P < 0.05) with 14:0 and 16:0, respectively. The addition of 5 mM 18:0 inhibited insulin secretion to 30 +/- 10% of basal (P < 0.003), and this effect was not caused by fatty acid interference with insulin assay.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Glucose control of basal insulin secretion in diabetes

Diabetologia ◽  
1977 ◽  
Vol 13 (2) ◽  
pp. 93-97 ◽  
Author(s):  
S. T. McCarthy ◽  
E. Harris ◽  
R. C. Turner
Keyword(s):  
Insulin Secretion ◽  
Glucose Control ◽  
Basal Insulin ◽  
Basal Insulin Secretion

scholarly journals Sweet Taste Receptors Regulate Basal Insulin Secretion and Contribute to Compensatory Insulin Hypersecretion During the Development of Diabetes in Male Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2112-2121 ◽  
Author(s):  
George A. Kyriazis ◽  
Kathleen R. Smith ◽  
Björn Tyrberg ◽  
Tania Hussain ◽  
Richard E. Pratley
Keyword(s):  
Insulin Secretion ◽  
Mouse Models ◽  
Basal Insulin ◽  
Sweet Taste ◽  
Human Islets ◽  
Continuous Exposure ◽  
Taste Receptors ◽  
Β Cells ◽  
Sweet Taste Receptors ◽  
Basal Insulin Secretion

β-Cells rapidly secrete insulin in response to acute increases in plasma glucose but, upon further continuous exposure to glucose, insulin secretion progressively decreases. Although the mechanisms are unclear, this mode of regulation suggests the presence of a time-dependent glucosensory system that temporarily attenuates insulin secretion. Interestingly, early-stage β-cell dysfunction is often characterized by basal (ie, fasting) insulin hypersecretion, suggesting a disruption of these related mechanisms. Because sweet taste receptors (STRs) on β-cells are implicated in the regulation of insulin secretion and glucose is a bona fide STR ligand, we tested whether STRs mediate this sensory mechanism and participate in the regulation of basal insulin secretion. We used mice lacking STR signaling (T1R2−/− knockout) and pharmacologic inhibition of STRs in human islets. Mouse and human islets deprived of STR signaling hypersecrete insulin at short-term fasting glucose concentrations. Accordingly, 5-hour fasted T1R2−/− mice have increased plasma insulin and lower glucose. Exposure of isolated wild-type islets to elevated glucose levels reduced STR expression, whereas islets from diabetic (db/db) or diet-induced obese mouse models show similar down-regulation. This transcriptional reprogramming in response to hyperglycemia correlates with reduced STR function in these mouse models, leading to insulin hypersecretion. These findings reveal a novel mechanism by which insulin secretion is physiologically regulated by STRs and also suggest that, during the development of diabetes, STR function is compromised by hyperglycemia leading to hyperinsulinemia. These observations further suggest that STRs might be a promising therapeutic target to prevent and treat type 2 diabetes.

Pulsatile insulin secretion accounts for 70% of total insulin secretion during fasting

1995 ◽  
Vol 269 (3) ◽  
pp. E478-E488 ◽  
Author(s):  
N. Porksen ◽  
S. Munn ◽  
J. Steers ◽  
S. Vore ◽  
J. Veldhuis ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Portal Vein ◽  
Basal Insulin ◽  
Deconvolution Analysis ◽  
Insulin Secretion In Vivo ◽  
Endogenous Insulin Secretion ◽  
Endogenous Insulin ◽  
Basal Insulin Secretion ◽  
Secretion Rates

The purpose of the present study was to determine the contributions of discrete insulin secretory bursts vs. basal insulin release to total insulin secretion in vivo. Quantification of the partitioning of pulsatile and basal insulin secretion is complicated by physiological delivery of these pulses into the portal vein and the absence of validated methods of measuring the rates of pulsatile and basal insulin secretion in vivo. We therefore 1) developed a canine model with chronically implanted portal vein catheters, 2) validated an established deconvolution technique as well as a novel direct catheterization technique (Clustcath) for measurement of pulsatile and nonpulsatile insulin secretion rates in this model, and 3) applied these methods to study insulin secretion in the overnight-fasted dog in vivo to determine the contribution of pulsatile vs. basal insulin secretion to total rates of endogenous insulin secretion. Rates of total, pulsatile, and nonpulsatile endogenous insulin secretion measured by Cluscath closely parallel those measured by deconvolution analysis (54 +/- 15 vs. 51 +/- 11, 38 +/- 12 vs. 36 +/- 11, and 16 +/- 4 vs. 14 +/- 4 pmol/min, respectively). Clustcath and deconvolution indicated that the majority of insulin was secreted as pulses (70 +/- 6 and 66 +/- 7%, respectively). These data infer that any process that selectively decreases the pulsatile component of insulin secretion (e.g., diabetes mellitus) will likely have a major impact on total insulin secretion.

Limited role for SREBP-1c in defective glucose-induced insulin secretion from Zucker diabetic fatty rat islets: a functional and gene profiling analysis

2006 ◽  
Vol 291 (5) ◽  
pp. E982-E994 ◽  
Author(s):  
Laura E. Parton ◽  
Patrick J. McMillen ◽  
Yingnian Shen ◽  
Elizabeth Docherty ◽  
Erin Sharpe ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Basal Insulin ◽  
Regulatory Element ◽  
Dominant Negative ◽  
Gene Profiling ◽  
Rat Islets ◽  
Zdf Rat ◽  
Element Binding Protein ◽  
Basal Insulin Secretion ◽  
Glucose Stimulated Insulin Secretion

Accumulation of intracellular lipid may contribute to defective insulin secretion in type 2 diabetes. Although Zucker diabetic fatty (ZDF; fa/fa) rat islets are fat-laden and overexpress the lipogenic master gene, sterol regulatory element binding protein 1c (SREBP-1c), the contribution of SREBP-1c to the secretory defects observed in this model remains unclear. Here we compare the gene expression profile of lean control ( fa/+) and ZDF rat islets in the absence or presence of dominant-negative SREBP-1c (SREBP-1c DN). ZDF islets displayed elevated basal insulin secretion at 3 mmol/l glucose but a severely depressed response to 17 mmol/l glucose. While SREBP-1c DN reduced basal insulin secretion from ZDF islets, glucose-stimulated insulin secretion was not improved. Of 57 genes differentially regulated in ZDF islets and implicated in glucose metabolism, vesicle trafficking, ion fluxes, and/or exocytosis, 21 were upregulated and 5 were suppressed by SREBP-1c DN. Genes underrepresented in ZDF islets were either unaffected ( Glut-2, Kir6.2, Rab3), stimulated (voltage-dependent Ca2+ channel subunit α1D, CPT2, SUR2, rab9, syt13), or inhibited ( syntaxin 7, secretogranin-2) by SREBP-1c inhibition. Correspondingly, SREBP-1c DN largely corrected decreases in the expression of the transcription factors Pdx-1 and MafA but did not affect the abnormalities in Pax6, Arx, hepatic nuclear factor-1α (HNF1α), HNF3β/Forkhead box-a2 (Foxa2), inducible cyclic AMP early repressor (ICER), or transcription factor 7-like 2 (TCF7L2) expression observed in ZDF islets. We conclude that upregulation of SREBP-1c and mild increases in triglyceride content do not explain defective glucose-stimulated insulin secretion from ZDF rats. However, overexpression of SREBP-1c may contribute to enhanced basal insulin secretion in this model.

Acute and chronic gastrin-releasing peptide decreases food intake in baboons

1985 ◽  
Vol 248 (5) ◽  
pp. R578-R583 ◽  
Author(s):  
D. P. Figlewicz ◽  
L. J. Stein ◽  
S. C. Woods ◽  
D. Porte
Keyword(s):  
Insulin Secretion ◽  
Food Intake ◽  
Basal Insulin ◽  
Low Dose ◽  
Chronic Administration ◽  
Gastrin Releasing Peptide ◽  
Total Food Intake ◽  
Total Food ◽  
Basal Insulin Secretion ◽  
Stimulation Of

Gastrin-releasing peptide (GRP) is a peptide structurally related to bombesin that appears to be localized to the mammalian gastrointestinal tract. This study examined the ability of GRP, when administered on either an acute or chronic basis, to suppress food intake in baboons. When administered at 8 micrograms/kg iv before a morning meal, GRP significantly suppressed both food intake and the postprandial rise of plasma glucose and insulin. GRP at doses of 1, 2, 4, and 8 micrograms/kg stimulated basal insulin secretion. Chronic administration of GRP (q.o.d. for 11 days) at a low dose before the A.M. meal resulted in suppression of the A.M. meal and an initial suppression of total food intake, which recovered before the end of the treatment period. In conclusion, GRP appears to be effective in acute suppression of food intake and stimulation of basal insulin secretion in the nonhuman primate.

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