Nonhuman Primate Models of Type 1 Diabetes Mellitus for Islet Transplantation

Table 1

DM induction in NHPs by STZ administration.

Author and publication year	Animals tested; (gender, age, and BW)	STZ dose	Solvent	Route of administration	Results
Theriault et al., 1999 [82]	Cyno (6–8 months, 1.0-2.0 kg),	150 mg/kg	0.9% NS	via SVAP	All persistently hyperglycemic (BG > 200 mg/dL; 9/11 serum C-P < 0.5 ng/mL, 60 days; 2/11 C-P at 0.9 ng/mL, 159 days); all without any observable clinical complications except transient nausea and vomiting
Shibata et al., 2002 [92]	Rhesus (female, 2.5–7.5 years, 4.2–6.8 kg)	STZ (Upjohn); G1: 100 mg/kg (); G2: 125 mg/kg (); G3: 150 mg/kg ()	Citric acid (pH 4.5)	via CVC	G1: none diabetic (unchanged basal insulin, NIPCs in islets was 7.7℅ of normal values); G2: all diabetic (IDDM) without mortality and hepatic/renal injury (NIPCs was 0.3℅ of normal values); G3: 2/7 dead (28.6℅ mortality), 5/7 diabetic (up to 3 weeks, no IPCs)
Koulmanda et al., 2003 [78]	Cyno (male, 3–6 years, 3.1–9.0 kg)	G1: 100 mg/kg (); G2: 55 mg/kg ()	0.9% NS	i.v.	All groups diabetic (IDDM, BG > 400 mg/dL, Serum C-P < 0.6 ng/mL, loss of BW, decreased NIPCs); G1: impaired liver/kidney functions, severe hepatic steatosis, and acute renal tubular injury; G2: normal liver/kidney functions, no histological changes
Tal et al., 2004 [95]	Cyno (4–6 years, ); Rhesus (8–12 years, ); Pigtail (2 years, )	STZ (Zanosar); 50–70 mg/kg	5% dextrose	Selective arterial injection	All diabetic (BG > 200 mg/dL, complete obliteration of β-cell, 20–270 days of duration); 1/14 dead (gastric dilatation); no abnormalities in liver and kidney
Rood et al., 2006 [91]	Cyno (male, 2-3 years, 2.7–4.1 kg)	G1: STZ (Sigma), 1250 mg/m^2 (); G2: STZ (Sigma), 60 mg/kg (); G3: STZ (Zanosar), 150 mg/kg ()	NM	i.v.	G1: all completely diabetic (BG > 200 mg/dL, C-P < 0.5 ng/mL, low NIPCs), with several AEs (vomiting, protein-losing nephropathy, and low ALB levels); G2: failed to loss complete β-cell function (C-P at 1.86 ng/mL), no AEs; G3: all completely diabetic (BG > 200 mg/dL, C-P < 0.5 ng/mL, low or no NIPCs), with only transient vomiting
He et al., 2011 [69]	Rhesus (3–6 years)	G1: single STZ ad. (80 mg/kg), ; G2: multiple STZ ad. (25 mg/kg for 5 consecutive days),	NM	i.v.	All groups diabetic; G1: lower C-P levels (<0.1 nmol/L) and probability of hypoglycemia (0.41); G2: relatively higher C-P levels (<0.5 nmol/L) and probability of hypoglycemia (0.80)
Zou et al., 2012 [96]	Cyno (male, 2.4–4.7 kg)	STZ (Sigma); G1: 100 mg/kg (); G2: 68 mg/kg (); G3: 60 mg/kg ()	Citric acid (pH 4.5)	i.v. (via saphenous vein)	G1 and G2: all diabetic (mean fasting BG > 22 mmol/L, low NIPCs, >8 months of duration), without any marked hepatic/renal injury; G3: one diabetic (fasting BG at 26.4 mmol/L, C-P at 28 pmol/L); the other nondiabetic (fasting BG at 5.7 mmol/L, C-P at 413 pmol/L)

Overview of published studies of STZ-induced diabetic models in NHPs.
NM: not mentioned; DM: diabetes mellitus; NHP: nonhuman primate; STZ: streptozotocin; BW: body weight; G: group; Cyno: cynomolgus monkey; Rhesus: rhesus monkey; Pigtail: pigtail macaque; NS: normal saline; SVAP: subcutaneous vascular access ports; CVC: central venous catheter; BG: blood glucose; C-P: c-peptide; IDDM: insulin-dependent diabetes mellitus; NIPCs: number of insulin-positive cells; i.v.: intravenous; ALB: albumin; AEs: adverse events; and ad.: administration.